3100 Hanover Street

Palo Alto, California, 94304

April 27, 2023

Dear Guardant Stockholder:

We are pleased to invite you to attend the Guardant Health, Inc. 2023 Annual Meeting of Stockholders to be held on Wednesday, June 14, 2023, at 9:30 a.m. Pacific Time, virtually at www.virtualshareholdermeeting.com/GH2023.

The last year was a breakthrough for us at Guardant Health in many ways. We continued to expand our core Guardant360^® franchise with another year of record sales. We gained Medicare reimbursement for our Guardant Reveal^™ test addressing both minimal residual disease (MRD) detection and recurrence monitoring in colorectal cancer (CRC), and also expanded its use to include early-stage breast and lung cancers. Towards the end of the year, we reached a historic milestone with positive results from ECLIPSE, an over 20,000 patient registrational study evaluating the performance of our blood test for detecting CRC in average-risk adults.

In our Oncology business, nearly nine years after we launched the first comprehensive liquid biopsy, Guardant360 continued to experience rapid growth in clinical volumes and revenues as we reinforced our market-leading position. On the regulatory front, we received approval for Guardant360^® CDx in Japan for tumor mutation profiling and several companion diagnostic indications, and in the United States as a companion diagnostic for ENHERTU^® in non-small cell lung cancer. Guardant Reveal volume grew by more than 250% as clinicians responded positively to the availability of the first tissue-free liquid biopsy for MRD testing. In addition, our Guardant360 TissueNext^™ assay for comprehensive genomic profiling gained Medicare reimbursement and grew rapidly during the year, broadening our offering to clinical customers.

Our screening program achieved a significant development goal with the successful readout of our ECLIPSE trial in CRC screening. Our Shield^™ test demonstrated 83% sensitivity for CRC detection at 90% specificity. This was the highest level of performance ever demonstrated by a blood-based cancer screening test in a large scale prospective clinical study. CRC screening continues to be one of the largest unmet medical needs in healthcare, with over 49 million eligible Americans remaining unscreened and at higher risk of CRC-related death. Lack of adherence to screening recommendations due to barriers associated with available test methods has been a major issue, but with our Shield LDT test, we have shown 90% test adherence, more than double the rate of fecal immunochemical testing (FIT), which is currently the most used colorectal cancer screening test in the United States. With the completion of our FDA submission in March 2023, we are well positioned to bring the first high-performance and high-adherence blood-based test to market for CRC screening. We continue to investigate multi-cancer screening to detect early-stage cancers where there is a clinical benefit from early detection and treatment. Specifically, in January 2022, we initiated the SHIELD LUNG study, a prospective, observational, multi-center basket study designed to enroll individuals undergoing cancer screening across multiple cancer types.

We also expanded our biopharma business, ending the year with over 150 partnerships to help bring the next generation of cancer therapeutics to patients sooner. In September 2022, we introduced GuardantINFINITY^™, a “smart liquid biopsy” assay that provides researchers with novel genomic and epigenomic insights into the tumor microenvironment and patient immune responses from a simple blood draw. We also expanded our international presence further with the opening of our labs in Vall d’Hebron in Spain and The Royal Marsden in the United Kingdom.

These breakthrough technologies and advancements are enabling us to continue to fulfill our commitment to help patients at all stages of cancer live longer and healthier lives. We thank all of our stakeholders for their continued support and confidence in our efforts to transform cancer care.

We hope that you will join us at our 2023 Annual Meeting of Stockholders on June 14, 2023. Your continuing interest in Guardant Health is very much appreciated.

Sincerely,

Helmy Eltoukhy

Chairperson of the Board of Directors

and Co-Chief Executive Officer

AmirAli Talasaz

Co-Chief Executive Officer

3100 Hanover Street

Palo Alto, California, 94304

NOTICE OF 2023 ANNUAL MEETING OF STOCKHOLDERS

TO BE HELD ON JUNE 14, 2023

To the Stockholders of Guardant Health, Inc.:

NOTICE IS HEREBY GIVEN that the 2023 Annual Meeting of Stockholders (the “Annual Meeting”) of Guardant Health, Inc., a Delaware corporation, will be held on Wednesday, June 14, 2023, at 9:30 a.m. Pacific Time, virtually at www.virtualshareholdermeeting.com/GH2023.

The Annual Meeting will be held for the following purposes:

These matters are more fully described in our proxy materials accompanying this Notice.

We know of no other matters to come before the Annual Meeting. Only stockholders who owned shares of common stock of Guardant Health, Inc. at the close of business on April 17, 2023 are entitled to notice of and to vote on matters brought for vote at the Annual Meeting or at any postponements or adjournments thereof.

You are cordially invited to attend the meeting conducted via live webcast, by registering at www.virtualshareholdermeeting.com/GH2023. You will not be able to attend the Annual Meeting in person. Whether or not you expect to attend, the Board of Directors respectfully requests that you vote your shares of common stock in the manner described in this proxy statement. You may revoke your proxy in the manner described in this proxy statement at any time before it has been voted at the meeting. Regardless of the number of shares of common stock you own, as a stockholder your role is very important, and the Board of Directors strongly encourages you to exercise your right to vote.

By order of the Board of Directors of Guardant Health, Inc.,

John Saia

Chief Legal Officer and Corporate Secretary

Palo Alto, California

April 27, 2023

TABLE OF CONTENTS

PROXY STATEMENT

INFORMATION CONCERNING VOTING AND SOLICITATION

General

Your proxy is solicited on behalf of the Board of Directors (the “Board”) of Guardant Health, Inc., a Delaware corporation (as used herein, “Guardant,” “Guardant Health,” “we,” “us” or “our”), for use at our 2023 annual meeting of stockholders (the “Annual Meeting”) to be held on Wednesday, June 14, 2023, at 9:30 a.m. Pacific Time, virtually at www.virtualshareholdermeeting.com/GH2023, or at any continuation, postponement or adjournment thereof, for the purposes discussed in this proxy statement and in the accompanying Notice of Annual Meeting and any other business properly brought before the Annual Meeting. Proxies are solicited to give all stockholders an opportunity to vote on matters properly presented at the Annual Meeting.

Virtual Annual Meeting. The Annual Meeting will be a virtual meeting of stockholders conducted via live audio webcast. You are invited to attend the Annual Meeting online. We believe that a virtual meeting provides expanded stockholder access and participation, as well as improved communications. You will be able to attend, vote and submit your questions online during the Annual Meeting. You will not be able to attend the Annual Meeting in person. Stockholders may attend the Annual Meeting online by logging onto www. virtualshareholdermeeting.com/GH2023 using the 16-digit control number included on your Notice of Internet Availability of Proxy Materials, on your proxy card, or on the voting instruction form provided by your broker, bank or other nominee.

Notice and Access Proxy Delivery. We have elected to provide access to our proxy materials over the Internet. Accordingly, we are sending a Notice of Internet Availability of Proxy Materials (the “Notice”) to most of our stockholders of record, and paper copies of the proxy materials to certain other stockholders of record. Brokers and other nominees who hold shares on behalf of beneficial owners will be sending their own similar Notice to such beneficial owners. All stockholders will have the ability to access the proxy materials on the website referred to in the Notice or request to receive a printed set of the proxy materials. You can find instructions on how to request a printed copy by mail or electronically on the Notice and on the website referred to in the Notice, including an option to request paper copies on an ongoing basis. On or about April 27, 2023, we intend to make this proxy statement available on the Internet and to commence mailing of the Notice to all stockholders entitled to vote at the Annual Meeting. We intend to mail this proxy statement, together with a proxy card, to those stockholders entitled to vote at the Annual Meeting who properly request paper copies of such materials, within three business days of such request.

Important Notice Regarding the Availability of Proxy Materials for the 2023 Annual Stockholder Meeting to be Held on June 14, 2023

Our proxy statement and 2022 Annual Report are available at www.proxyvote.com. This website address contains: the Notice of Annual Meeting, the proxy statement and proxy card sample, and the 2022 Annual Report. You will need your 16-digit control number that is included on your Notice, on your proxy card, or on the voting instruction form provided by your

1

broker, bank or other nominee, to access these materials. You are encouraged to access and review all of the important information contained in the proxy materials before voting.

Who Can Vote, Outstanding Shares

Record holders of our common stock as of the close of business on April 17, 2023, the record date for the Annual Meeting (the “Record Date”), are entitled to notice of and to vote at the Annual Meeting on all matters to be voted upon. As of the Record Date, there were 102,764,757 shares of our common stock outstanding. On each matter presented to our stockholders for vote, the holders of common stock are entitled to one vote per share held as of the Record Date.

Voting of Shares

The method of voting by proxy differs (1) depending on whether you are viewing this proxy statement on the Internet or receiving a paper copy and (2) for shares held as a record holder and shares held in “street name.”

Record Holder. If you hold your shares of common stock as a record holder and you are viewing this proxy statement on the Internet, you may vote by submitting a proxy over the Internet by following the instructions on the website referred to in the Notice previously mailed to you. If you hold your shares of common stock as a record holder and you are reviewing a paper copy of this proxy statement, you may vote your shares by completing, dating and signing the proxy card that was included with the proxy statement and promptly returning it in the preaddressed, postage paid envelope provided to you, or by submitting a proxy over the Internet or by telephone by following the instructions on the proxy card.

Hold in Street Name. If you hold your shares of common stock in street name, which means your shares are held of record by a broker, bank or nominee, you will receive a Notice from your broker, bank or other nominee that includes instructions on how to vote your shares. Your broker, bank or nominee will allow you to deliver your voting instructions over the Internet and may also permit you to vote by telephone. In addition, you may request paper copies of the proxy statement and proxy card from your broker by following the instructions on the Notice provided by your broker.

General. The Internet and telephone voting facilities will close at 11:59 p.m. EDT on June 13, 2023. If you vote through the Internet, you should be aware that you may incur costs to access the Internet, such as usage charges from telephone companies or Internet service providers and that these costs must be borne by you. If you vote by Internet or telephone, then you need not return a written proxy card by mail.

Voting at the Virtual Annual Meeting. To attend and vote at the Annual Meeting you need to access the meeting via live audio webcast at www.virtualshareholdermeeting.com/GH2023 using the 16-digit control number included on your Notice, on your proxy card or on the voting instruction form. Attendance at the Annual Meeting will not, by itself, result in any vote or revocation of a prior vote. You must follow the instructions at www.virtualshareholdermeeting.com/GH2023 to vote your shares at the Annual Meeting.

2

YOUR VOTE IS VERY IMPORTANT. You should submit your proxy even if you plan to attend the Annual Meeting online. If you properly give your proxy and submit it to us in time to vote, one of the individuals named as your proxy will vote your shares as you have directed.

All shares entitled to vote and represented by properly submitted proxies (including those submitted electronically, telephonically and in writing) received before the polls are closed at the Annual Meeting, and not revoked or superseded, will be voted at the Annual Meeting in accordance with the instructions indicated on those proxies. If no direction is indicated on a proxy, your shares will be voted as follows:

The proxy gives each of Helmy Eltoukhy, AmirAli Talasaz and John Saia discretionary authority to vote your shares in accordance with their best judgment with respect to all additional matters that might come before the Annual Meeting.

If you receive more than one proxy card or Notice, it means you hold shares that are registered in more than one account. To ensure that all of your shares are voted, sign and return each proxy card or, if you submit a proxy by telephone or the Internet, submit one proxy for each proxy card or Notice you receive.

Revocation of Proxy

If your shares are held of record, you may change or revoke your proxy at any time before your proxy is voted at the Annual Meeting by taking any of the following actions:

3

Written notices of revocation and other communications with respect to the revocation of proxies by record holders should be addressed to:

Guardant Health, Inc.

3100 Hanover Street

Palo Alto, California 94304

Attention: Corporate Secretary

If your shares are held in the name of a broker, bank, or other nominee, you may change or revoke your voting instructions by following the instructions of your broker, bank, or other nominee contained on the Notice.

Broker Non-Votes

Brokers, banks or other nominees who hold shares of common stock in “street name” for a beneficial owner of those shares typically have the authority to vote in their discretion on “routine” proposals when they have not received instructions on how to vote on such matter from the beneficial owners. However, brokers are not allowed to exercise their voting discretion with respect to the election of directors or for the approval of matters that are considered “non-routine” without specific voting instructions from the beneficial owner. If you hold your shares in street name and do not provide voting instructions to your broker on how to vote on the election of directors or other “non-routine” proposals, your broker cannot exercise discretion to vote you shares and your shares will be considered to be “broker non-votes” and will not be voted on such matters. Accordingly, if your broker holds your common stock in “street name,” your broker will vote your shares on the election of directors and other “non-routine” proposals only if you provide instructions to your broker on how to vote your shares by following the procedures outlined in the voting instruction form sent to you by your broker. Only Proposal No. 2 (ratifying the appointment of our independent registered public accounting firm) is considered a routine matter on which your broker may vote without instruction from you as the beneficial owner. Proposal No. 1 (election of directors) and Proposal No. 3 (advisory vote to approve named executive officer compensation) are considered non-routine matters, and without your instruction, your broker cannot vote your shares for either of Proposal No. 1 or Proposal No. 3.

Quorum and Votes Required

The inspector of elections appointed for the Annual Meeting will tabulate votes cast by proxy, telephone and via Internet at www.proxyvote.com as of 11:59 p.m. EDT on June 13, 2023. The inspector of elections will also tabulate votes cast at www.virtualshareholdermeeting.com/GH2023 during the Annual Meeting and will determine whether a quorum is present. In order to constitute a quorum for the conduct of business at the Annual Meeting, the holders of a majority of the shares of common stock issued and outstanding and entitled to vote at the Annual Meeting must be present or represented by proxy at the Annual Meeting. On the Record Date, there were 102,764,757 shares of common stock entitled to vote at the Annual Meeting. Shares that abstain from voting on any proposal, or that are represented by broker non-votes, will be treated as shares that are present and entitled to vote at the Annual Meeting for purposes of determining whether a quorum is present.

4

Proposal No. 1: Election of Directors. A plurality of the votes cast in the election of directors at the Annual Meeting is required for the election of directors. You may vote “FOR” or “WITHHOLD” your vote on any nominee. The three Class II director nominees receiving the highest number of “FOR” votes will be elected. Broker non-votes are considered votes not cast and thus will have no effect on the outcome of the election of directors.

Proposal No. 2: Ratification of Independent Registered Public Accounting Firm. The affirmative vote of the holders of a majority of the votes cast at the Annual Meeting is required for the ratification of the appointment of Deloitte as our independent registered public accounting firm. You may vote “FOR” or “AGAINST” or “ABSTAIN”. The number of votes “FOR” must exceed the number of votes “AGAINST” for the proposal to pass. Abstentions are considered to be votes not cast on this proposal and thus will have no effect. Brokers generally have discretionary authority to vote on the ratification of our independent registered public accounting firm, thus broker non-votes are not expected to result from the vote on Proposal No. 2. Any broker non-votes would be considered votes not cast and thus would have no effect.

Proposal No. 3: Advisory Vote to Approve Named Executive Officer Compensation. The affirmative vote of the holders of a majority of the votes cast at the Annual Meeting is required for determining approval on an advisory basis of the compensation of our named executive officers, as described in the “Compensation Discussion and Analysis,” executive compensation tables and accompanying narrative disclosures in our proxy materials. You may vote “FOR” or “AGAINST” or “ABSTAIN”. The number of votes “FOR” must exceed the number of votes “AGAINST” for the proposal to pass. Abstentions and broker non-votes are considered to be votes not cast on this proposal and thus will have no effect. This vote is advisory and not binding on us, our Board, or our Compensation Committee.

In their discretion, the proxy holders named in the proxy are authorized to vote on any other matters that may properly come before the Annual Meeting and at any continuation, postponement or adjournment thereof. The Board knows of no other items of business that will be presented for consideration at the Annual Meeting other than those described in this proxy statement. In addition, no stockholder proposal or nomination was received on a timely basis, so no such matters may be brought to a vote at the Annual Meeting.

Vote Recommendation

Our Board of Directors unanimously recommends that you vote:

5

Details Regarding the Virtual Annual Meeting

Similar to last year, the Annual Meeting will again be held virtually this year via live interactive audio webcast on the Internet. You will be able to attend, vote and submit your questions during the Annual Meeting by logging onto www.virtualshareholdermeeting.com/GH2023. You will not be able to attend the Annual Meeting in person.

Access to the Annual Meeting

The live audio webcast of the Annual Meeting will begin promptly at 9:30 a.m. Pacific Time. Online access to the audit webcast will open approximately 15 minutes prior to the start of the Annual Meeting to allow time for our stockholders to log in and test their devices’ audio system. We encourage our stockholders to access the meeting in advance of the designated start time.

Log-In Instructions

Instructions on how to connect to the Annual Meeting, participate and demonstrate proof of stock ownership are posted at www.virtualshareholdermeeting.com/GH2023. To participate in the Annual Meeting, you will need to log-in using the 16-digit control number on your Notice, proxy card or voting instruction form.

Technical Assistance

Beginning 15 minutes prior to the start of and during the Annual Meeting, we will have a support team ready to assist stockholders with any technical difficulties they may have accessing or hearing the virtual meeting. If you encounter any difficulties accessing the virtual meeting during the check-in or meeting time, please call the technical support number that will be posted on the Virtual Shareholder Meeting log in page.

Submitting Questions at the Annual Meeting

Stockholders may submit questions and vote at www.virtualshareholdermeeting.com/GH2023 during the Annual Meeting. You will need to enter the 16-digit control number received with your Notice, proxy card or voting instruction form as proof of stock ownership in order to be able to submit questions and vote at our Annual Meeting. After the business portion of the Annual Meeting concludes and the meeting is adjourned, we will hold a Q&A session during which we intend to answer the questions submitted during the Annual Meeting that are pertinent to us and that are submitted in accordance with the Rules of Conduct for the Annual Meeting, as time permits. The Rules of Conduct will be posted on the virtual meeting web portal. Substantially similar questions will be answered only once. To promote fairness, efficient use our resources and to ensure all stockholder questions are able to be addressed, we will respond to no more than two questions from a single stockholder.

Solicitation of Proxies

Our Board is soliciting proxies for the Annual Meeting from our stockholders. We will bear the entire cost of soliciting proxies from our stockholders. In addition to the solicitation of proxies by delivery of the Notice or proxy statement by mail, we will request that brokers,

6

banks and other nominees that hold shares of our common stock, which are beneficially owned by our stockholders, send Notices, proxies and proxy materials to those beneficial owners and secure those beneficial owners’ voting instructions. We will reimburse those record holders for their reasonable expenses. We do not intend to hire a proxy solicitor to assist in the solicitation of proxies. We may use several of our regular employees, who will not be specially compensated, to solicit proxies from our stockholders, either personally or by telephone, Internet, facsimile or special delivery letter.

Stockholder List

A list of stockholders eligible to vote at the Annual Meeting will be available for inspection, for any purpose germane to the Annual Meeting, at our corporate headquarters for a period of no less than ten days ending on the day prior to the Annual Meeting date. Please contact our Corporate Secretary at CorpSecretary@guardanthealth.com if you are interested in viewing the list. The list of stockholders will also be made available during the Annual Meeting at www.virtualshareholdermeeting.com/GH2023.

7

CORPORATE GOVERNANCE

Corporate Governance Focus and Stockholder Outreach

Over the course of the last year, the Board has been actively engaged in a comprehensive review of its corporate governance practices and in taking steps to strengthen and enhance those practices in response to stockholder feedback. These steps have included increasing the size of the Board from seven to nine directors and increasing the gender diversity of the Board (which now includes three women directors). Most recently, the Board also made a number of meaningful enhancements to the Company’s corporate governance structure. In February 2022, our Board amended our Governance Committee Charter to enhance the Governance Committee’s oversight of corporate social responsibility, including ESG policies and practices and revised our Code of Conduct to increase the breadth and specificity of standards to be upheld by all directors, officers and employees of the Company, including adding and refining guidelines regarding conflicts of interest, business records, gifts and favors, antitrust practices, political contributions, environmental protection, and personal conduct and social media practices.

We recognize the value of a robust stockholder outreach program. We engage in regular, constructive dialogue with our stockholders on matters relevant to our business, including corporate governance, executive compensation, strategy, environmental, social and governance issues, and human capital management. During the third and fourth quarters of 2022 and the first quarter of 2023, we contacted our top 75 stockholders, representing more than 86% of the Company’s outstanding shares of common stock. We ultimately spoke with 21 stockholders representing approximately 57% of the Company’s outstanding shares of common stock. Please see “Compensation Discussion and Analysis – Stockholder Outreach” for more details regarding our outreach, stockholder feedback and responses by the Board and its committees.

Board Composition

The Board currently has nine members. Consistent with the Board’s commitment to Board refreshment, on June 30, 2022, Steve Krognes was appointed to the Board as a Class III director to serve for a term expiring at our 2024 annual meeting of stockholders. On February 21, 2023, Musa Tariq was appointed to the Board as a Class I director to serve for a term expiring at our 2025 annual meeting of stockholders.

8

The following provides summary information about each continuing director and director nominee and reflects their committee assignments as of April 27, 2023.

  Chair         Member

AC Audit Committee CC Compensation Committee N&CG Nominating & Corporate Governance Committee

The Board is divided into three classes (Class I, Class II and Class III) with staggered terms of three years each and holding office until his or her successor is duly elected and qualified, or until his or her earlier resignation or removal. The term of one class expires at each annual meeting of stockholders.

Statistics for Nine Continuing Directors and Director Nominees (As of Our Annual Meeting)

9

In accordance with Nasdaq Stock Market (“Nasdaq”) rules, the following Board Diversity Matrix sets forth the required diversity statistics for our existing directors:

Diversity of Skills and Expertise for Directors as of Our Annual Meeting

The skills matrix below identifies our continuing directors’ prominent experiences and qualifications by name. Each director brings his or her own unique background and range of expertise, knowledge and experience which provides an appropriate and diverse mix of qualifications necessary for our Board to effectively fulfill its oversight responsibilities. By its nature, the information contained in this summary is not intended to be exhaustive but aims to convey the general breadth of experience and qualifications that our directors bring to their work on our Board to oversee strategy, performance, culture and risk at the Company.

10

Board Skills of Nine Continuing Directors

Senior Executive Leadership

●

●

●

●

●

●

●

●

●

Other Public Company Board Experience

●

●

●

●

●

Corporate Strategy / M&A

●

●

●

●

●

●

●

●

Financial / Accounting or Audit Experience

●

●

●

●

●

●

Healthcare Industry Experience

●

●

●

●

●

●

●

Sales / Marketing Experience

●

●

●

●

●

●

Risk Management and Compliance

●

●

●

●

●

●

●

Sustainability and ESG

●

●

●

●

●

Cybersecurity / Technology

●

●

●

●

●

●

●

Global / International Experience

●

●

●

●

●

●

●

Our Nominating and Corporate Governance Committee (the “Governance Committee”) is responsible for determining Board membership qualifications and for selecting, evaluating and recommending to the Board nominees for annual election to the Board and to fill vacancies as they arise. When considering whether directors and nominees have the experience, qualifications, attributes or skills to enable the Board to satisfy its oversight responsibilities effectively in light of our business and structure, the Governance Committee and the Board evaluate each individual in the context of the Board as a whole, with the objective of assembling a team that can best perpetuate the success of the business and represent

11

stockholder interests through the exercise of sound judgment using its diversity of experience, thought, backgrounds and cultures. Directors and nominees should have a high level of personal and professional integrity, strong ethics and values and the ability to make mature business judgments. The Governance Committee maintains Director Qualification Standards for selecting nominees and for considering stockholder recommended nominees, which are included in this proxy statement as Appendix A. In determining whether to recommend a director for re-election, the Governance Committee also considers the director’s past attendance at meetings and participation in and contributions to the Board’s activities. Our directors possess a range of diverse skills, backgrounds, experience and viewpoints that we believe are integral to an effective board of directors. Detailed information about each individual’s qualifications, experience, skills and expertise along with select professional and community contributions can be found above and in the section entitled “Proposal 1: Election of Directors” in this proxy statement. We believe that our directors provide an appropriate mix of experience, diversity and skills relevant to the size and nature of our business.

The Governance Committee is mindful of the policies regarding board service of certain investors and proxy advisory firms, which policies were developed due to concerns that “overboarded” directors face excessive time commitments and challenges in fulfilling their duties. Mr. Clark may be deemed “overboarded” under certain policies. In 2022, Mr. Clark reduced the number of boards he serves on from six to five. The Governance Committee reviewed and considered the contributions of Mr. Clark to the Board and noted his strong attendance, preparedness and engagement at Board and committee meetings, as well as his leadership as our Lead Independent Director. The Governance Committee also noted Mr. Clark’s valuable and extensive public company director experience and expertise.

The Governance Committee will consider stockholder recommendations of candidates on the same basis as it considers all other candidates. Stockholders may propose director nominees by adhering to the advance notice procedures described in the section entitled “Other Matters: Stockholder Proposals and Nominations” in this proxy statement and must include all information as required under our Amended and Restated Certificate of Incorporation (the “Certificate of Incorporation”) and Amended and Restated Bylaws (the “Bylaws”), and any other information that would be required to solicit a proxy under federal securities laws. We may request from the recommending stockholder or recommending stockholder group such other information as may reasonably be required to determine whether each person recommended by a stockholder or stockholder group as a nominee meets the minimum director qualifications established by our Board and is independent based on applicable laws and regulations. The Governance Committee may also establish procedures, from time to time, regarding submission of candidates by stockholders and others.

Director Independence

Our Governance Committee and our Board have undertaken a review of the Board’s composition, the composition of Board committees and the independence of each director. Based upon information concerning each director’s background, employment and affiliations, including family relationships, the Board has affirmatively determined that each of Ian Clark, Vijaya Gadde, Meghan Joyce, Samir Kaul, Steve Krognes, Myrtle Potter and Musa Tariq is independent, as defined under the applicable listing requirements and rules of Nasdaq and

12

the Securities and Exchange Commission (the “SEC”), and that each of them and their respective family members have no material relationship with us, commercial or otherwise, that would interfere with the exercise of their independent judgment in carrying out the responsibilities of a director. Drs. Eltoukhy and Talasaz were determined to not be independent due to their service as our Co-CEOs. In making these determinations, the Board considered the current and prior relationships that each non-employee director has with us and all other facts and circumstances the Board deemed relevant in determining their independence, including the beneficial ownership of our capital stock by each non-employee director.

Board Leadership Structure

Our Board has determined that at this time it is in the best interests of the Company and our stockholders to have Helmy Eltoukhy, our Co-CEO, serve as our Chairperson of the Board, coupled with a strong lead independent director, Ian Clark. Dr. Eltoukhy was appointed as Chairperson of the Board on August 5, 2021, succeeding AmirAli Talasaz in this role. We believe having one of our senior executives serve as Chairperson promotes responsibility and accountability, and that our Board benefits from having a Chairperson with his extensive understanding of our business and the unique challenges we face. The Board believes that this structure best facilitates consistent leadership direction and long-term strategic planning, while building a cohesive corporate culture that speaks with a single voice.

Our Board also recognizes the value and importance of a strong independent lead director with clearly delineated responsibilities. The independent directors have appointed Ian Clark to serve as our lead independent director. As set forth in our Corporate Governance Guidelines, Mr. Clark, as our independent lead director, has clearly delineated and comprehensive duties, including:

Our Board will continue to evaluate its leadership structure in order to ensure it aligns with and supports the evolving needs and circumstances of Guardant and its stockholders.

Corporate Governance Guidelines

Our Board has adopted corporate governance guidelines covering, among other things, the duties and responsibilities of and independence standards applicable to our directors and Board committee structures and responsibilities. These guidelines are available on the “Corporate Governance” section of our website at https://investors.guardanthealth.com.

13

Attendance by Members of the Board at Meetings

Our Board held six meetings and acted by written consent three times during the year ended December 31, 2022. During 2022, all of our then incumbent directors attended at least 75% of the combined total of (i) all Board meetings and (ii) all meetings of committees of the Board of which the incumbent director was a member. The membership of each standing committee in 2022 and the number of meetings held during 2022 are identified in the table below.

* Does not include action by written consent

Currently, we do not maintain a formal policy regarding director attendance at the Annual Meeting; however, it is expected that, absent compelling circumstances, each of our directors will attend our Annual Meeting. Each of our then-seven incumbent directors attended our 2022 Annual Meeting of Stockholders (the “2022 Annual Meeting”).

Executive Sessions

Our non-management directors meet regularly in executive sessions without management, to consider such matters as they deem appropriate. Our lead independent director, Mr. Clark, presides over all executive sessions.

Board Committees

We currently have three standing committees: Audit Committee, Compensation Committee and Governance Committee. From time to time, the Board may form a new committee or disband a current committee, depending on the circumstances. The charters of all three of our standing Board committees are available on our website under the “Corporate Governance – Governance Documents” section at https://investors.guardanthealth.com.

Audit Committee

Our Audit Committee currently consists of Steve Krognes, Meghan Joyce and Myrtle Potter, with Mr. Krognes serving as chair. Mr. Krognes joined the Audit Committee as the

14

chair upon his appointment to the Board effective June 30, 2022. Mr. Kaul served as chair of the Audit Committee from the date of our 2022 Annual Meeting until June 30, 2022. Ian Clark served on the Audit Committee until our committee refreshment effective May 1, 2022. Our Board has determined that each of these directors is independent as defined by the applicable rules of the Nasdaq and the SEC, and that each member of the Audit Committee meets the financial literacy and experience requirements of the applicable SEC and Nasdaq rules. In addition, our Board has determined that each of Messrs. Krognes and Kaul, and Mss. Joyce and Potter is an “audit committee financial expert” as defined by the SEC. The Audit Committee met four times and did not act by written consent during the year ended December 31, 2022.

Our Audit Committee charter requires that the Audit Committee oversee our corporate accounting and financial reporting processes. The primary responsibilities and functions of our Audit Committee are, among other things, as follows:

Compensation Committee

Our Compensation Committee currently consists of Vijaya Gadde, Samir Kaul and Myrtle Potter, with Ms. Gadde serving as chair. Ian Clark served on the Compensation Committee until our committee refreshment effective May 1, 2022. Our Board has determined that each of these directors is independent under Nasdaq rules and that each qualifies as a “non-employee director” under Section 16 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). The Compensation Committee met six times and did not act by written consent during the year ended December 31, 2022.

15

The Compensation Committee’s responsibilities include, among other things:

Since October 2019, the Compensation Committee has engaged Aon’s Human Capital Solutions Practice, a division of Aon plc (“Aon”), as independent compensation consultants to provide advice and guidance on the design of our executive compensation programs and practices. Aon attends Compensation Committee meetings when invited and meets with the Compensation Committee without management. Aon provides the Compensation Committee with third-party data and analysis as well as advice and expertise on competitive compensation practices and trends, executive compensation plans and program designs, and proposed executive and director compensation levels. Aon reports directly to the Compensation Committee and, as directed by the Compensation Committee, works with management and the chair of the Compensation Committee.

For 2022 compensation, Aon assisted the Compensation Committee with the following:

Aon did not provide any additional services to the Company during 2022.

The Compensation Committee regularly reviews the services provided by its outside consultants, and it has assessed the independence of Aon consistent with SEC rules and Nasdaq listing standards. In doing so, the Compensation Committee considered each of the factors set forth by the SEC and Nasdaq with respect to a compensation consultant’s independence. The Compensation Committee also considered the nature and amount of work performed for the Compensation Committee and the fees paid for those services in relation to the firm’s total revenues. On the basis of its consideration of the foregoing and other relevant factors, the Compensation Committee has determined that Aon is independent, and that no conflicts of interest exist between the Company and Aon.

16

Nominating and Corporate Governance Committee

Our Governance Committee currently consists of Ian Clark, Meghan Joyce, and Steve Krognes, with Mr. Clark serving as chair. Samir Kaul served on the Governance Committee until our committee refreshment effective May 1, 2022. Our Board has determined that each of these directors is independent under Nasdaq rules. The Governance Committee met four times and acted by written consent once during the year ended December 31, 2022.

In response in part to stockholder feedback, in February 2022, the Board reviewed and enhanced the oversight responsibilities of the Governance Committee. The Governance Committee’s responsibilities include, among other things:

Risk Oversight

The Audit Committee of the Board is primarily responsible for overseeing our risk management processes on behalf of the Board. The Audit Committee receives reports from management on at least a quarterly basis regarding our assessment of risks. In addition, the Audit Committee reports regularly to the Board, which also considers our risk profile, about material issues affecting the quality or integrity of our financial statements, compliance with legal or regulatory requirements, the performance or independence of the independent auditor, the performance of the Company’s internal audit function, and other matters that the Audit Committee deems appropriate. The Audit Committee and the Board focus on the most significant risks we face and our general risk management strategies. While the Board oversees our risk management, management is responsible for day-to-day risk management processes. Our Board expects management to consider risk and risk management in each business decision, to proactively develop and monitor risk management strategies and processes for day-to-day activities and to effectively implement risk management strategies adopted by the Audit Committee and the Board. We believe this division of responsibilities is

17

the most effective approach for addressing the risks we face and that our Board’s leadership structure, which also emphasizes the independence of the Board in its oversight of its business and affairs, supports this approach. The standing committees of the Board retain primary responsibility for risk oversight in the following key areas:

Each of our committees periodically provide updates to the Board regarding risk management issues and management’s response.

Business Code of Conduct and Ethics

We have adopted a written Code of Conduct that applies to our directors, officers and employees, including our principal executive officer, principal financial officer, principal accounting officer or controller, or persons performing similar functions. In February 2022, our Board amended the Code of Conduct to increase the breadth and specificity of standards to be upheld by all directors, officers and employees of the Company, including adding and refining guidelines regarding conflicts of interest, business records, gifts and favors, antitrust practices, political contributions, environmental protection, and personal conduct and social media practices. We have posted a current copy of the code on our website, https://investors.guardanthealth.com. In addition, we intend to post on our website all disclosures that are required by law or the listing standards of Nasdaq concerning any amendments to, or waivers from, any provision of the code.

Environmental, Social and Governance

Guardant’s Values. Each day at Guardant starts and ends with putting the patient first. We are a team of diverse, passionate, and curious individuals, motivated to transform cancer care for patients at all stages of the disease. Guided by our core values, our commitment to advancing breakthrough science and giving patients the opportunity to live healthier lives are central to how we operate. Even as these values have evolved, we have never wavered from our commitment to putting the patient first.

18

Our Core Values

Environmental, Social and Governance (ESG) Commitment. Our vision is to transform cancer care by creating impactful diagnostic tools that will be affordable and accessible to far more patients around the world. We are driven by an intense passion to dramatically change the course of cancer patients’ journeys. Our frustration with the data-starved status quo and our strong desire to improve human health shapes our unique culture. Our mission — to conquer cancer — is at the heart of our ESG commitment and fully integrated into our business strategy.

Guided by our core values, our commitment to advancing breakthrough science and giving patients the opportunity to live healthier lives are central to how we operate and are foundational to our approach to corporate responsibility. We believe that to serve patients well, it is important to also act responsibly in our relationships with our employees, our communities and the environment. Therefore, we are committed to: (1) providing meaningful work and development opportunities to our employees; (2) striving to recruit, hire and retain a talented and diverse team of people who align with our values and fostering a diverse, inclusive, and equitable workplace; (3) conducting our business with the highest professional and ethical standards and operating with integrity and mutual respect; (4) maintaining a well-developed environmental, health and safety program, which is reinforced through rigorous policies, education and engagement of our employees and internal and external periodic audits; (5) making it easy and affordable to complete our tests; and (6) investing in environmental sustainability and responsible supply chain operations.

In an effort to capture and communicate on our goals and recent accomplishments, we will release our inaugural ESG annual report (“ESG Report”) in May 2023. We look forward to enchancing and expanding on our ESG Report in the years to come.

19

Grants and Giving. We sponsor and support numerous non-profits and patient advocacy groups and our employees donate their time. Our contributions help to support the work of non-profit organizations of all sizes, working in areas such as cancer research and patient support, community wellness and scientific education, and supporting the mission to accelerate access to innovation for cancer patients.

Safety and Wellness. We are committed to providing a safe and secure work environment and maintaining environmental, health and safety policies that seek to promote the health and safety of our employees and patients. We mandate continual training programs, and we have a robust employee wellness program that recognizes and supports the importance of personal health and work-life balance. We are committed to rewarding, supporting, and developing the employees who make it possible to deliver on our strategy. To that end, we offer a comprehensive total rewards package that includes market-competitive fixed and/or variable pay, broad-based equity grants and bonuses, access to medical, dental, vision and life insurance benefits, disability coverage, fertility subsidies, retirement savings plans, paid time off and family leave, caregiving support, fitness, cellphone and internet reimbursements, and mental health and other wellness benefits.

Governance. We evaluate input from our stockholders and consider their independent oversight of management and our long-term strategy. As part of our commitment to constructive engagement with investors, we evaluate and respond to the views voiced by our stockholders. Our dialogue has led to enhancements in our corporate governance, ESG, and executive compensation activities, which we believe are in the best interest of the Company and our stockholders. In February 2022, our Board amended our Governance Committee Charter to enhance the Governance Committee’s oversight of corporate social responsibility, including ESG policies and practices.

Communications with our Board

Any interested person, including any stockholder, may communicate with our Board by written mail addressed to Guardant Health, Inc. Board of Directors, c/o Corporate Secretary, 3100 Hanover Street, Palo Alto, California, 94304. We encourage stockholders to include proof of ownership of our stock in their communications. The corporate secretary will review the communications and forward them to the Board or the relevant committee of the Board, unless the communication is primarily commercial in nature, relates to an improper or irrelevant topic, or is unduly hostile, threatening, illegal or otherwise inappropriate.

20

DIRECTOR COMPENSATION

Our Director Compensation Program is intended to fairly compensate our non-employee directors for the time and effort necessary to serve on our Board, in a manner that is competitive and serves the best interests of the Company and our stockholders.

Process for Determining Director Compensation. Decisions regarding the non-employee director compensation program are approved by our full Board based on recommendations by the Compensation Committee. The Compensation Committee reviews the total compensation of our non-employee directors and each element of our director compensation program each year, with this review usually scheduled before our annual stockholder meeting. The Compensation Committee consults with its independent compensation consultant periodically as to the competitive position of our director compensation program, both in terms of the compensation amount and with respect to the program’s design, against those of our peers (information about our peer group is on page 47).

The Board adopted its current equity-only compensation program, described below, effective as of June 12, 2020, the date of our 2020 annual stockholders’ meeting. The compensation for our Board members is aligned with long-term value creation because it consists solely of stock option and restricted stock unit awards that do not vest as to any of the underlying shares until one-year after the grant date. By using a program that is entirely based on stock awards, the Board has established that a compensation program that fully aligns their interests with those of our stockholders. Our directors do not receive cash compensation for their service as directors, but we pay their reasonable expenses incurred for attending meetings. The Compensation Committee did not recommend to the Board any adjustments to our director compensation program for 2022.

The following is a summary of our director compensation program that was adopted in June 2020 and remained in effect for 2022:

Initial Awards (each, an “Initial Award”)

Annual Awards (each, an “Annual Award”)

21

Annual Lead Independent Director Award (each, a “LID Award”)

The Initial Award is granted to each non-employee director who is initially elected or appointed to serve on the Board and each Initial Award vests and becomes exercisable (as applicable) as to 25% of the shares subject to such award on the first anniversary of the director’s election to the Board, and as to the remaining 75% of the shares subject to the Initial Award in substantially equal installments on each monthly anniversary of the director’s election to the Board thereafter, subject to continued service through the applicable vesting date.

The Annual Award is granted on the date of each annual stockholders’ meeting to non-employee directors who have served on the Board for at least six months prior to the date of such annual stockholders’ meeting. Each Annual Award vests and become exercisable (as applicable) in full on the earlier to occur of (i) the one-year anniversary of the applicable grant date and (ii) the date of the next annual meeting of the Company’s stockholders following the grant date, subject to continued service through the applicable vesting date.

The LID Award is granted on the date of each annual stockholders’ meeting to the non-employee director who has served on the Board for at least six months as of the date of such annual stockholders’ meeting and who will also serve as Lead Independent Director of the Board immediately following such meeting. Each LID Award will vest in full on the earlier to occur of (i) the one-year anniversary of the applicable grant date and (ii) the date of the next annual meeting of the Company’s stockholders following the grant date, subject to continued service through the applicable vesting date. Our Board decided that the additional LID Award is appropriate given the significant role and scope of the responsibilities of the Board’s Lead Independent Director, such as responsibilities related to leading meetings of independent directors, providing input on meeting agendas, advising our co-CEOs as to quantity, quality and timeliness of information and materials, providing feedback to our co-CEOs on the co-CEOs’ evaluation, and leading the Board evaluation process.

In addition, each Initial Award, Annual Award and LID Award will vest in full immediately prior to the director’s death, disability, termination without cause, or a change in control (as defined in the 2018 Incentive Award Plan (the “2018 Plan”)).

Any compensation payable to a director will comply with the director annual compensation limit set forth in our 2018 Plan (currently, an annual limit of $750,000 per director).

Director Compensation Table. The following table contains information concerning the compensation received by our non-employee directors during the year ended December 31, 2022. Directors who are also employees do not receive compensation for service on our

22

Board (in addition to the compensation payable for their service as our employees). Drs. Eltoukhy and Talasaz are not included in the table below because they did not receive any additional compensation for their service on our Board. Drs. Eltoukhy’s and Talasaz’s 2022 compensation is presented in the Summary Compensation Table found on page 60.

On June 30, 2022, Steve Krognes was appointed to the Board as a Class III director to serve for a term expiring at our 2024 annual meeting of stockholders. Mr. Krognes received his Initial Award on August 9, 2022 in connection with his initial appointment to the Board.

2022 DIRECTOR COMPENSATION TABLE

23

PROPOSAL 1:

ELECTION OF DIRECTORS

Board Nominees

Pursuant to our Certificate of Incorporation and our Bylaws, the total number of directors constituting the Board is fixed from time to time by the Board. There are currently nine authorized directors and nine persons serving as directors.

The Board is divided into three classes (Class I, Class II and Class III) with staggered terms of three years each and holding office until his or her successor is duly elected and qualified, or until his or her earlier resignation or removal. Each class contains as nearly as possible an equal number of directors. The term of one class expires at each annual meeting of stockholders; thus, directors typically stand for election after three years, unless they are filling an unexpired term. The current term of office of our Class II Directors expires at the Annual Meeting, while the term for our Class III Directors will expire at our 2024 annual meeting of stockholders and the term for our Class I Directors expires at our 2025 annual meeting of stockholders. On June 30, 2022, Steve Krognes was appointed to the Board as a Class III director to serve for a term expiring at our 2024 annual meeting of stockholders. On February 21, 2023, Musa Tariq was appointed to the Board as a Class I director, effective as of March 6, 2023, to serve for a term expiring at our 2025 annual meeting of stockholders.

Based upon the recommendation of our Governance Committee, the Board has nominated Ian Clark, Meghan Joyce and Samir Kaul, each a current Class II Director, for re-election at the Annual Meeting. Each director elected at the Annual Meeting will serve a three-year term expiring at the 2026 annual meeting of stockholders and until his or her successor is duly elected and qualified as a Class II Director, or until his or her earlier death, resignation or removal. At the Annual Meeting, proxies cannot be voted for a greater number of individuals than the three nominees named in this proxy statement.

The Board and the Governance Committee believe the skills, qualities, attributes and experience of our directors provide us with business acumen and a diverse range of perspectives to engage each other and management to effectively address our evolving needs and represent the best interests of our stockholders.

Vacancies on the Board, including any vacancy created by an increase in the size of the Board, may be filled only by a majority of the directors remaining in office, even though less than a quorum of the Board, or a sole remaining director. A director elected by the Board to fill a vacancy will serve until the next election of the class of directors for which such director was chosen and until such director’s successor is elected and qualified, or until such director’s earlier retirement, resignation, disqualification, removal or death.

If any nominee should become unavailable for election prior to the Annual Meeting, an event that currently is not anticipated by the Board, the proxies will be voted in favor of the election of a substitute nominee or nominees proposed by the Board or the number of directors may be reduced accordingly. Each nominee has agreed to serve if elected and the Board has no reason to believe that any nominee will be unable to serve.

24

Information about Class II Director Nominees

Set forth below is biographical information for each nominee and a summary of the specific qualifications, attributes, skills and experiences which led the Board to conclude that each nominee should serve on the Board at this time.

Class II Director with Term Expiring at the 2023 Annual Meeting

25

26

Information about Other Directors Not Standing for Election at this Meeting

Directors who will continue to serve after the Annual Meeting are listed below.

Class III Director with Term Expiring at the 2024 Annual Meeting

27

Class I Director with Term Expiring at the 2026 Annual Meeting

28

29

EXECUTIVE OFFICERS

The following are our executive officers as of the Record Date.

The following sets for the biographical information of our Executive Officers. Biographical information pertaining to Helmy Eltoukhy, who is our Chairperson of the Board and our Co-CEO, and AmirAli Talasaz, who is a member of the Board and our Co-CEO, may be found in the section above entitled “Proposal 1: Election of Directors – Information about Other Directors Not Standing for Election at this Meeting – Class III Director with Term Expiring at the 2024 Annual Meeting”.

Michael Bell. Mr. Bell has served as our Chief Financial Officer since January 2021. He most recently served as the Chief Financial Officer of CareDx, Inc., a precision medicine company focused on transplantation, from April 2017 to December 2020. From January 2016 to March 2017, Mr. Bell served as the Chief Financial Officer of Metabiota, Inc., a company that develops and sells risk analytics products focused on infectious disease. From May 2012 to January 2016, he served as the Chief Financial Officer of Singulex, Inc., a clinical diagnostics company. Prior to that, Mr. Bell held leadership and executive positions within Novartis, including with Novartis Diagnostics, a global provider of blood screening solutions, where he served as Chief Financial Officer from 2011 to 2012, and Senior Director, Global Head of Finance from 2008 to 2011. Mr. Bell also previously worked for several years in public accounting with both Ernst & Young and Deloitte, UK. He holds a Bachelor of Science degree in Mathematics with Computing from the University of Leicester in the United Kingdom and is a Fellow of the Institute of Chartered Accountants in England & Wales.

Craig Eagle, M.D. Dr. Eagle has served as our Chief Medical Officer since April 2021. He most recently served as Vice President of Medical Affairs Oncology for Genentech, a company that uses human generic information to develop, manufacture and sell medicines for serious conditions, from 2019 to 2021, where he oversaw the medical programs across the oncology portfolio and developed innovative cancer trials and strategies in personalized health care. Prior to Genentech, Dr. Eagle has held several positions in the U.S. and internationally at Pfizer, from 2009 to 2019, including global head of the Oncology Medical and Outcomes Group. In this role, he oversaw the worldwide medical programs and development of numerous commercially successful drugs. Dr. Eagle currently serves on the Board of Directors for Generex Biotechnology and NuGenerex Immuno-Oncology. Dr. Eagle

30

graduated from medical school at the University of New South Wales in Sydney, Australia and received his general internist training at Royal North Shore Hospital in Sydney. Dr. Eagle completed his specialist training in hemato-oncology and laboratory hematology at Royal Prince Alfred Hospital in Sydney and was granted Fellowship in the Royal Australasian College of Physicians (FRACP) and the Royal College of Pathologists Australasia (FRCPA).

Christopher Freeman. Mr. Freeman has served as our Chief Commercial Officer since June 2021. He most recently served as Vice President of the HIV Business Unit at Gilead Sciences, Inc., leading the $13 billion HIV treatment and prevention business, from January 2020 to June 2021. During the COVID-19 pandemic, Mr. Freeman led the Emergency Use Authorization for Veklury (remdesivir) to treat COVID-19. Mr. Freeman previously worked at Elan Pharmaceuticals from 2008 to 2011 where he was commercial lead for Elan’s Alzheimer’s pipeline products, and from 2001 to 2008, he worked at Genentech where he led marketing for their oncology product, Rituxan, and Xolair for patients suffering from asthma and severe allergies. Mr. Freeman is a member of the National Board of Directors for Dream Foundation, a national dream-granting organization for terminally ill adults and their families. Mr. Freeman served in the U.S. Army for five years, first enlisting as a Lieutenant and was promoted to Captain before being honorably discharged in 2001. Mr. Freeman graduated from the United States Military Academy at West Point.

Kumud Kalia. Mr. Kalia has served as our Chief Information Officer since January 2021. He most recently served as Chief Information and Technology Officer as well as other executive roles at Cylance, Inc., from March 2018 to June 2019, and previously served as Chief Information Officer at Akamai Technologies from October 2011 to February 2018. Prior to Akamai, Mr. Kalia worked at Direct Energy, an energy and services business operating in the U.S. and Canada, from March 2005 to January 2011, and where at the time of his departure he was the Chief Information Officer and Executive Vice President of Customer Operations. Earlier in his career, Mr. Kalia was Vice President and Chief Information Officer of the Business Markets Group of Qwest Communications International from 2002 to 2004 and served as Chief Information Officer for Dresdner Group in North America from 1998 to 2002. He has also performed in technology, operations and strategy roles at various investment banks. Mr. Kalia holds a Master’s degree in Information and Cyber Security from the University of California, Berkeley, an honors degree in Electronic Engineering from Bangor University, is a chartered engineer, and is a Fellow of both the Institution of Engineering and Technology and the British Computer Society.

Amelia Merrill. Ms. Merrill has served as our Senior Vice President, People, since August 2021, and prior to that as our Vice President, People, since May 2017. Prior to joining Guardant, she served as the Senior Vice President, People Strategy at Risk Management Solutions (RMS). She has also been an Advisory Board Member at Gild and RolePoint, and an Advisor for PeopleTech Partners and Wepow.

John Saia. Mr. Saia has served as our Chief Legal Officer and Corporate Secretary since April 2022, and prior to that as our Senior Vice President, General Counsel and Corporate Secretary since May 2020. He most recently served as Senior Vice President, General Counsel and Corporate Secretary of WageWorks, Inc., an administrator of consumer-directed benefits, from January 2019 until its acquisition by HealthEquity, Inc. in August 2019, and as General Counsel and Corporate Secretary for AcelRx Pharmaceuticals,

31

Inc., a specialty pharmaceutical company, from April 2018 to January 2019. Mr. Saia led legal and compliance activities worldwide for both WageWorks and AcelRx. Prior to that, he spent more than a decade serving in numerous legal and compliance leadership roles at McKesson Corporation, ending his tenure in April 2018 as its Corporate Secretary and Associate General Counsel. In addition to holding positions at several highly respected law firms, Mr. Saia also held roles at the U.S. Securities and Exchange Commission and the U.S. Department of Justice. Mr. Saia graduated cum laude from Santa Clara University and holds a Juris Doctorate from The George Washington School of Law.

32

EXECUTIVE COMPENSATION

COMPENSATION DISCUSSION AND ANALYSIS

This Compensation Discussion and Analysis (“CD&A”) discusses the principles and objectives underlying our policies and decisions with respect to the compensation of our named executive officers (“NEOs”) and other material factors relevant to an analysis of these policies and decisions regarding our 2022 executive compensation program. This CD&A is intended to be read in conjunction with the tables that immediately follow this section, which provide further compensation information for our 2022 NEOs:

Quick CD&A Reference Guide

I.  BUSINESS AND COMPENSATION OVERVIEW

Company Overview

We are a leading precision oncology company focused on helping conquer cancer globally through the use of our proprietary tests, vast data sets and advanced analytics. We believe our tests can transform cancer care by unlocking insights that will help patients at all stages of the disease, including at its earliest stages, when it’s most treatable. For patients with advanced-stage cancer, we have commercially launched Guardant360 laboratory developed test, or LDT, and Guardant360 CDx, the first comprehensive liquid biopsy test approved by the U.S. Food and Drug Administration, or the FDA, to provide tumor mutation profiling with solid tumors and to be used as a companion diagnostic in connection with non-small cell lung cancer, or NSCLC, and breast cancer. We have also launched the Guardant360 TissueNext tissue test for advanced-stage cancer, the Guardant Reveal blood test to detect residual and recurring disease in early-stage cancer patients, and the

33

Guardant360 Response blood test to predict patient response to immunotherapy or targeted therapy eight weeks earlier than current standard-of-care imaging.

We also collaborate with biopharmaceutical companies in clinical studies by providing the above-mentioned tests, as well as the GuardantOMNI blood test for advanced-stage cancer, and the GuardantINFINITY blood test, launched in September 2022, which is a next-generation smart liquid biopsy that provides new, multi-dimensional insights into the complexities of tumor molecular profiles and immune response to advance cancer research and therapy development. Using data collected from our tests, we have also developed our GuardantINFORM platform to help biopharmaceutical companies accelerate precision oncology drug development through the use of this in-silico research platform to unlock further insights into tumor evolution and treatment resistance across various biomarker-driven cancers.

In May 2022, we launched the Shield LDT test to address the needs of individuals eligible for colorectal cancer screening. From a simple blood draw, Shield uses a novel multimodal approach to detect colorectal cancer signals in the bloodstream, including DNA that is shed by tumors. In addition, in December 2022, we announced positive results from ECLIPSE, an over 20,000 patient registrational study evaluating the performance of our Shield blood test for detecting colorectal cancer in average-risk adults. We also expect to expand into lung and multi-cancer screening with our investigational, next-generation Shield assay.

We have implemented a set of values and core beliefs for the Company to drive cultural change and create an environment centered on patient care, collaboration, inclusion and innovation. For more information on our values, please see “Corporate Governance—Environmental, Social and Governance—Guardant’s Values”.

We believe our tests can expand the scope of precision oncology to earlier stages of the disease, improve patient outcomes and lower healthcare costs.

Stockholder Engagement

General. We recognize the value of a robust stockholder outreach program. We engage in regular, constructive dialogue with our stockholders on matters relevant to our business, including corporate governance, executive compensation, strategy, environmental, social and governance issues and human capital management. We believe that our approach to engaging openly with our stockholders drives increased corporate accountability, improves decision making, and ultimately creates long-term value.

34

Our Stockholder Engagement Cycle

Robust Stockholder Engagement

Advisory Vote on Executive Compensation and Actions Taken in Response

At our 2022 Annual Meeting, we received approximately 61.2% support of the votes cast on our Say-on-Pay proposal. In addition to the outreach conducted in the weeks leading up to our 2022 Annual Meeting, following our review of the results of the shareholder advisory vote at the 2022 Annual Meeting, we again reached out to stockholders to solicit feedback on our investors’ concerns with the compensation of our NEOs. As part of this outreach program, during the third and fourth quarters of 2022 and the first quarter of 2023, we contacted our top 75 stockholders, representing more than 85% of the Company’s outstanding shares of common stock. We ultimately spoke with 21 stockholders representing approximately 57% of the Company’s outstanding shares of common stock, including at least five institutions that voted “against” our Say-on-Pay proposal last year. Seven of these stockholders, representing approximately 30% of the Company’s outstanding shares of common stock, declined and indicated a meeting with the Company was not necessary, while 14 of these stockholders, representing approximately 27% of the Company’s outstanding shares of common stock, engaged with us and provided substantive feedback.

The Chief Legal Officer, our Vice President of Investor Relations and other members of the corporate legal team participated in this effort on behalf of the Company. All feedback received was shared and discussed with the Compensation Committee, the Governance Committee and the full Board.

Response to Stockholder Feedback. Below is a summary of the principal feedback we received since our 2022 Annual Meeting and the changes made to our executive compensation program in response to this feedback, which we believe are beneficial to the creation of sustained long-term stockholder value.

35

36

The following provides additional details regarding how our Compensation Committee implemented the changes described in the table above:

37

Clawback Policy

Additionally, while our co-CEOs and Chief Financial Officer are subject to any recovery rights that are provided under applicable laws, including the Sarbanes-Oxley Act, and the standard terms of the 2018 Plan, we intend to adopt a compensation recovery policy as required under the Dodd-Frank Act. We are reviewing the final clawback rule adopted by the SEC that implements the applicable provisions of the Dodd-Frank Act and the Nasdaq’s related proposed listing standard, in each case relating to recoupment of incentive-based compensation. The Company will implement its clawback policy in accordance with the new listing standard when the new listing standard becomes final.

Co-CEO Compensation Decisions – Waiver Letters

Drs. Eltoukhy and Talasaz entered into waiver of compensation agreements (the “Waiver Letters”) with the Company in connection with the grant of PSUs in May 2020 that vest based on the achievement of robust stock price hurdles (the “Founders’ 2020 Performance Awards”). Pursuant to the Waiver Letters, each executive agreed to forego any annual bonuses or long-term or equity-based compensatory awards, and reduced their annual base salaries to $1, during the seven-year term of the Founders’ 2020 Performance Awards (the “Waiver Period”), which is scheduled to expire in May 2027, unless otherwise terminated earlier in accordance with the terms of the Waiver Letters. Accordingly, the total compensation received by each of Drs. Eltoukhy and Talasaz in fiscal year 2022 was $1, which represents each executive’s 2022 base salary.

Realized Pay Demonstrates Pay for Performance Alignment

A core component of our compensation philosophy is to incentivize our executive officers by creating a strong link between their individual performance, the Company’s operating and financial performance and the compensation they earn. To show the alignment of pay outcomes with performance, it is useful to illustrate the amounts realizable as of December 31, 2022 and 2021 relative to the reported amounts of NEO compensation set by the Compensation Committee for the year.

Realizable pay shows this relationship because it reflects the actual value of equity awards to be received by NEOs as of the fiscal year end, and fluctuates with performance and with increases or decreases in stock price. For this reason, contrasting reported pay with realizable pay provides a meaningful demonstration of the pay for performance alignment of our executive compensation program.

Drs. Eltoukhy and Talasaz entered into the Waiver Letters (as defined below) with the Company in connection with the grant of PSUs in May 2020 that vest based on the achievement of robust stock price hurdles. Pursuant to the Waiver Letters, each executive agreed to forego any annual bonuses or long-term or equity-based compensatory awards, and reduced their annual base salaries to $1, during the seven-year term of the PSUs.

38

The following chart demonstrates, for each of the past two years, the relationship between the reported and realizable values of the NEOs’ aggregate annual equity grants.

The values shown as “Reported” reflect the reported amounts of stock and option awards as shown in the 2021 and 2022 Summary Compensation Tables. The equity grants include stock options, RSUs and PSUs.

The “Realizable” value shown for the equity grants represents the number of RSUs and PSUs multiplied by the stock price per share on the last trading day of 2021 or 2022, as applicable. The “Realizable” value shown for stock options is $0 because the exercise price of all options granted is greater than the year end stock price in both years. Because of the decrease in the share price that is a key component of the equity value, the realizable equity value represented substantially less than the reported value, demonstrating the direct link between performance and the potential pay outcome.

Compensation Objectives

The core elements of the Compensation Committee’s executive compensation philosophy are as follows:

39

2022 Select Business Highlights

We had a year of great progress in 2022, with solid growth in our financial results and strong advancement in our product development program. We achieved record revenues and volumes during the year, launched new offerings in minimal residual disease with multi cancer Reveal and expanded market access for our tests. We also launched our Smart Liquid Biopsy platform, which we believe will drive the next chapter of growth for our oncology business and enable significant R&D efficiency and operating leverage. With the approval of our first companion diagnostic in breast cancer and expanded payor coverage, we are poised for continued growth in the year ahead.

In May 2022, we launched the Shield LDT test to address the needs of individuals eligible for colorectal cancer screening. From a simple blood draw, Shield uses a novel multimodal approach to detect colorectal cancer signals in the bloodstream, including DNA that is shed by tumors. Our research and development results to date indicate that somatic signatures alone may be insufficient for detection of early-stage cancers with high sensitivity. For this reason, we have incorporated epigenomic signatures to enhance the performance of our Shield assay in these settings.

In December 2022, we announced positive results from our pivotal ECLIPSE study for colorectal cancer, an over 20,000 patient registrational study evaluating the performance of our Shield blood test for detecting colorectal cancer in average-risk adults. The test demonstrated 83% sensitivity in detecting individuals with colorectal cancer. Specificity was 90% in both individuals without advanced neoplasia and in those who had a negative colonoscopy result. These results exceed the performance criteria set forth by the Centers for Medicare and Medicaid Services, or CMS, for reimbursement. This test also demonstrated 13% sensitivity in detecting advanced adenomas. Based on these study results, in March 2023, we submitted to the FDA the final module of our premarket approval, or PMA, applicable for Shield, our blood test to screen for colorectal cancer. While we await FDA review, we are aggressively continuing our screening research and development efforts for lung and additional cancers.

We also expect to expand into lung and multi-cancer screening with our investigational, next-generation Shield assay. To clinically validate the performance of our next-generation Shield blood test in detecting lung cancer in high-risk individuals ages 50-80, in January 2022, we enrolled the first patient in a nearly 10,000-patient prospective, registrational study, which we refer to as the SHIELD LUNG study. The study is anticipated to run in approximately 100 centers in the United States and Europe.

We believe our product portfolio, once completed, will address the full continuum of cancer care and has utility in both the clinical and biopharmaceutical markets.

40

Key highlights include the following:

Financial Results

Net loss attributable to common stockholders was $654.6 million for 2022, as compared to $405.7 million for the corresponding prior year period. Net loss per share attributable to common stockholders was $6.41 for 2022, as compared to $4.00 for the corresponding prior year period. Non-GAAP net loss was $435.4 million for 2022, as compared to $251.7 million for the corresponding prior year period. Non-GAAP net loss per share was $4.26 for 2022, as compared to $2.48 for the corresponding prior year period.

We define our non-GAAP measures as the applicable GAAP measure adjusted for the impacts of stock-based compensation and related employer payroll tax payments, changes in estimated fair value of noncontrolling interest liability, adjustments relating to redeemable noncontrolling interest, contingent consideration, acquisition related expenses, amortization of intangible assets, fair value adjustments on marketable equity securities, impairment of other assets, and other non-recurring items. See Appendix B for a reconciliation of non-GAAP information.

41

Key Aspects of the 2022 Executive Compensation Program

Base Salaries. Drs. Eltoukhy and Talasaz received annual base salaries of $1 following the May 2020 grant of the Founders’ 2020 Performance Awards. The base salaries of the other NEOs were determined pursuant to arm’s length negotiations upon hire and are adjusted by the Compensation Committee as appropriate.

Annual Bonuses. 2022 annual bonuses for the NEOs other than Drs. Eltoukhy and Talasaz (who were not eligible to receive a 2022 annual bonus pursuant to the terms of the Waiver Letters) were determined based on our achievement against oncology product development milestones and screening research and development measures, representing a combined 60% of the target bonus opportunity (together, the “Operational Performance Component”), financial performance metrics, representing 35% of the target bonus opportunity (the “Financial Performance Component”), and a metric based on employee retention, representing 5% of the target bonus opportunity.

To establish these targets and goals, the Compensation Committee, with the input of the senior leadership team, and taking into account other corporate achievements and developments, set the targets at levels that it considered rigorous and challenging and that took into account the relevant risks and opportunities.

In the view of the Compensation Committee, for 2022, it was critically important to advance our oncology product program and our screening research and development program, and thus the Compensation Committee placed greater emphasis on the Operational Performance Component. Specifically, 30% of the target bonus opportunity related to oncology products and performance with respect to new product reimbursement, new product clinical volume, the launch of Guardant Reveal and the launch of upgraded Guardant360. Another 30% related to screening research and development performance, including the ECLIPSE study read out, data presentation regarding Guardant SHIELD and the launch of LDT.

The Financial Performance Component was comprised of:

(i) a revenue goal, which represented 25% of the target bonus opportunity, and

(ii) adjusted EBITDA and gross margin goals, each of which represent 5% of the target bonus opportunity.

The Compensation Committee set a rigorous revenue target substantially above the prior-year level, reflecting nearly 27% growth. In addition, there was rigor in the performance curve, as the 25% of target bonus opportunity attributed to revenue performance would be forfeited if we didn’t achieve at least 20% growth from the prior year. The targets for gross margin and adjusted EBITDA were also set at levels that the Compensation Committee viewed as challenging to achieve. The Compensation Committee incorporated these measures in the 2022 annual bonus program in order to focus executive officers on the critical strategic priorities of top line revenue growth and operating profitability.

The target for employee retention was also considered challenging, in light of the highly competitive market for talent in our industry in the San Francisco Bay area.

42

Based on our 2022 oncology product development and research-based achievements and financial results, the Compensation Committee determined that overall achievement relative to the goals was 67% of target.

2022 Long-Term Incentives. 2022 equity grants for our NEOs other than Drs. Eltoukhy and Talasaz (who were not eligible to receive a 2022 equity grant pursuant to the terms of the Waiver Letters) consisted of stock options and restricted stock units, with the target value divided evenly between these awards. Long-term incentive equity awards are prospective in nature and intended to tie a substantial portion of an executive’s pay to creating long-term stockholder value. The Compensation Committee structures the long-term incentive opportunity to motivate executive officers to achieve multi-year strategic goals and deliver sustained long-term value to stockholders, and to reward them for doing so.

As part of the continuing evolution of the executive compensation program, in early 2023, the Compensation Committee began to incorporate performance-based equity when it granted PSUs to the NEOs, other than our co-CEOs. See below for a description of the 2023 PSUs.

II. COMPENSATION PHILOSOPHY AND OBJECTIVES

Compensation Philosophy

The Compensation Committee believes that a well-designed compensation program should align executive interests with the drivers of growth and stockholder returns, including by supporting the Company’s achievement of its primary business goals and the Company’s ability to attract and retain employees whose talents, expertise, leadership and contributions are expected to build and sustain growth in long-term stockholder value. As a result, we maintain a strong pay-for-performance orientation in our compensation program.

To achieve these objectives, the Compensation Committee regularly reviews our compensation policies and program design to ensure that they are aligned with the interests of our stockholders and our business goals, and that the total compensation paid to our executives is fair, reasonable and competitive for our size and stage of development. Specifically, the Compensation Committee targets base salaries, annual cash bonuses, and annual long-term equity incentive awards for our executive officers around the market median for our peer group, with variability in actual payments based on corporate and individual performance.

Compensation Objectives

Key objectives of our compensation programs include the following:

43

The Compensation Committee believes using equity for the long-term incentives creates strong alignment between the interests of executive officers and the interests of our stockholders because it gives executive officers and stockholders a common interest in stock price performance. Granting equity also fosters an ownership culture among executive officers by making them stockholders with a personal stake in Guardant Health’s growth and success.

In recruiting our executive officers and determining competitive pay levels, the Compensation Committee references the amounts and compensation structures of executive officers in the companies in our compensation peer group and in industry surveys.

The Compensation Committee strives to make the incentives in our executive compensation program straightforward and the programs transparent and understandable, so that our executive officers, as well as our stockholders, know what they are working toward, and what they will receive if they succeed. The Compensation Committee seeks to design programs that give participants a clear line of sight to the selected metrics and sufficient control over the performance toward the goals, to motivate them effectively for achieving our business objectives and to reward them appropriately, as a means of executing our strategy.

44

Compensation Program Governance

The Compensation Committee assesses the effectiveness of our executive compensation program from time to time and reviews risk mitigation and governance matters, which includes maintaining the following best practices:

45

III.  COMPENSATION DETERMINATION PROCESS

Role of the Compensation Committee

The Compensation Committee establishes our compensation philosophy and objectives; determines the structure, components and other elements of the executive compensation program; and reviews and approves the compensation of the NEOs or recommends it for approval by the Board. The Compensation Committee structures the executive compensation program to accomplish its articulated compensation objectives in light of the compensation philosophy described above.

Toward the end of each year, the Compensation Committee reviews the elements of our executive compensation program to verify the alignment of the program with our business strategy and with the items that we believe drive the creation of stockholder value, and to determine whether any changes would be appropriate.

At the beginning of the new year, after the end of applicable annual performance periods, the Compensation Committee evaluates achievement relative to performance targets, and examines whether it would be appropriate to apply negative discretion to the initial earned amounts in order to take relevant factors into consideration, and determines corresponding payouts earned.

The Compensation Committee obtains input from executive officers regarding the annual operating plan, expected financial results, anticipated milestone results and related risks. Based on this information, the Compensation Committee establishes the performance-based metrics and targets for the annual incentive plan. For each metric, the Compensation Committee sets appropriate threshold and maximum levels of performance designed to motivate achievement without incentivizing excessive risk-taking. With the input of the co-CEOs, the Compensation Committee also establishes the compensation for all the other executive officers. The Compensation Committee sets the compensation for each of our NEOs and makes recommendations to the full Board generally at its meetings in the first quarter of each year.

46

Role of the Independent Compensation Consultant

The Compensation Committee recognizes that there is value in procuring independent, objective expertise and counsel in connection with fulfilling its duties, and pursuant to its charter, the Compensation Committee has the authority to select and retain independent advisors and counsel to assist it with carrying out its duties and responsibilities. The Compensation Committee has exercised this authority to engage Aon as its independent compensation consultant, and has worked with Aon to develop a compensation peer group, provide a competitive market analysis of the base salary, annual cash incentive awards and long-term incentive compensation of our executive officers compared against the compensation peer group, report on share utilization, and review other market practices and trends.

While the Compensation Committee took into consideration the review and recommendations of Aon as well as the practices of our compensation peer group when making decisions about our executive compensation program, ultimately, the Compensation Committee made its own independent decisions in determining our executives’ compensation.

Compensation Peer Groups and Peer Selection Process

Relevant market and benchmark data provide a solid reference point for making decisions and very helpful context, even though, relative to other companies, there are differences and unique aspects of the Company. The Compensation Committee takes into consideration the structure and components of, and the amounts paid under, the executive compensation programs of other, comparable peer companies, as derived from public filings and other sources when making decisions about the structure and component mix of our executive compensation program.

The Compensation Committee, with the assistance of Aon, developed a peer group in 2021 for use in connection with decisions about 2022 executive compensation using the following criteria: sector (commercial biopharma and medical technology companies, with an emphasis on oncology and diagnostics where possible), revenue, and market capitalization. As of April 2021, the Company’s revenue was at the 9th percentile of the peer group revenue for fiscal year, and its market capitalization was at the 68th percentile of the peer group market capitalization.

Based on these criteria and considerations, the Compensation Committee approved a peer group for decisions relating to 2022 executive compensation that consisted of the following 16 companies:

47

Based on the peer analysis performed by Aeon in 2021 for the purpose of selecting our 2022 peer group, Amarin Corp. plc, bluebird bio, inc., Genomic Health, Inc. and Moderna, inc. were removed, and 10x Genomics, Inc., Exelixis, Inc. and Invitae Corporation were added. In general, the removed peer companies no longer fit the selection criteria, as described above and further below, while the additions reflect companies with financial and industry characteristics more similar to our company.

In addition to the criteria above, the Compensation Committee also referenced general and specific industry surveys from other sources. The Compensation Committee determined that the appropriate market reference continues to be the 50th percentile. The market data are used as a reference point and to provide information on the range of competitive pay levels and current compensation practices in our industry.

We believe that the compensation practices of our peer group provided us with appropriate compensation reference points for evaluating and determining the compensation of our named executive officers during 2022. Consistent with best practices for corporate governance, the Compensation Committee will review our peer group annually. In mid-2022, the Compensation Committee engaged Aon to develop a new peer group that will be referenced in making decisions regarding executive compensation for 2023.

Role of the Co-Chief Executive Officers

The Compensation Committee works with our co-CEOs to set the target compensation of each of our other NEOs. As part of this process, the co-CEOs evaluate the performance of the other executive officers annually and make recommendations to the Compensation Committee in the first quarter of the year regarding the compensation of each other executive officer.

The input of the co-CEOs is particularly important. The Compensation Committee gives significant weight to their recommendations in light of their greater familiarity with the day-to-day performance of their direct reports and the importance of incentive compensation in driving the execution of managerial initiatives developed and led by the co-CEOs. Nevertheless, the Compensation Committee or the Board of Directors makes the ultimate determination regarding the compensation for the executive officers.

IV. COMPENSATION PROGRAM COMPONENTS

2022 Components in General

In order to achieve its executive compensation program objectives, the Compensation Committee utilizes the compensation components set forth in the chart below. The Compensation Committee regularly reviews each executive officer’s total compensation opportunity to ensure it is consistent with its compensation philosophy and objectives and that the component is serving a purpose in supporting the execution of our strategy.

48

49

Base Salary

Base salaries provide fixed compensation to executive officers and help us to attract and retain the executive talent needed to lead the business and maintain a stable leadership team. Base salaries are individually determined according to each executive officer’s areas of responsibility, role and experience, and they vary among executive officers based on a variety of considerations, including skills, experience, achievements and the competitive market for the position.

For newly hired executive officers, the Compensation Committee establishes initial base salaries through arm’s-length negotiations at the time the executive officer is hired, considering the position and the executive’s experience, qualifications and the competitive market.

From time to time, the Compensation Committee considers and approves base salary adjustments for executive officers. The main considerations for a salary adjustment are similar to those used in initially determining base salaries, but may also include change in the competitive market, change of role or responsibilities, recognition for achievements or market trends. The Compensation Committee approved 2022 base salary increases for Messrs. Bell and Freeman and Dr. Eagle, each of which represented annual increases made in the normal course to align with the competitive market. The Compensation Committee approved a 2022 base salary increase for Mr. Saia in connection with his promotion to Chief Legal Officer.

The base salaries for each of our executive officers in effect at the end of 2022, and the adjustment from 2021, are as follows:

Annual Incentive Plan

The annual incentive plan for executive officers is a cash plan that rewards NEOs for the achievement of key short-term objectives. In particular, the plan offers incentives to the NEOs other than the co-CEOs to accomplish certain specified product development and research-based milestones and short-term financial results that the Compensation Committee views as key steps in the execution of our overall business strategy, with the intent ultimately of increasing stockholder value. In connection with the Founders’ 2020 Performance Awards granted to Drs. Eltoukhy and Talasaz in May 2020 and the long-term opportunity presented

50

by such grants, each of Drs. Eltoukhy and Talasaz formally agreed to waive their right to receive an annual cash incentive opportunity until 2027.

In the Compensation Committee’s view, the most senior executive officers have the greatest responsibility for the performance of the Company, and consequently, the annual incentive plan for such executive officers utilizes only pre-established objective Company performance measures, with no individual discretionary component (other than with respect to the application of negative discretion to reduce earned amounts).

Performance Measures

The amount of the payout, if any, under the annual incentive plan is based on our achievement against (1) oncology product development milestones and screening research and development measures, representing a combined 60% of the target bonus opportunity (together, the “Operational Performance Component”), (2) financial performance metrics, representing 35% of the target bonus opportunity (the “Financial Performance Component”), and (3) a metric based on employee retention, representing 5% of the target bonus opportunity.

In the view of the Compensation Committee, for 2022, it was critically important to advance our oncology product program and our screening research and development program, and thus the Compensation Committee placed greater emphasis on the Operational Performance Component. Specifically:

The financial measures selected by the Compensation Committee—Revenue, Gross Margin and Adjusted EBITDA—also remained very important, as they focus executive officers on the critical strategic priorities of top line revenue growth and operating profitability.

51

Finally, given the importance of retaining our human capital, and the highly competitive market for talent in the San Francisco Bay area, the Compensation Committee tied 5% of the target award to retention of our valued employees.

Target, Threshold and Maximum Performance Levels

The Compensation Committee set the performance metric targets at levels that it considered rigorous and challenging and that took into account the relevant risks and opportunities. More specifically, the Compensation Committee reviewed the relevant operational goals in light of the Company’s plans, as well as the financial objectives set as a result of the detailed budgeting process, and assessed various factors related to the achievability of these targets, including the risks associated with various macroeconomic factors, including macroeconomic factors, and the risks of achieving specific actions that underlie the targets and the implied performance relative to prior years.

Considering these factors, the Compensation Committee set the 2022 targets for the Operational Performance Components at levels or with timing in accordance with the Company’s strategic and operational plans. With respect to the Financial Performance Component, the Compensation Committee also set the 2022 target for revenue at a 26.6% growth rate over total revenue in 2021 and the target for 2022 gross margin at a 520 basis point decrease over the gross margin in 2021.

Having set the targets, the Compensation Committee also set the threshold and maximum performance levels for both the Operational Performance Component and the Financial Performance Component. For the 2022 milestone measures, the threshold level of performance generally involved achieving the goal later or in a lower amount, and maximum performance generally involved achieving it sooner or in a higher amount. For the 2022 financial measures, the Compensation Committee set the threshold at a high-performance level of approximately 95% of the target for revenue. The thresholds for gross margin and adjusted EBITDA loss were also set at high performance levels. The Compensation Committee set the maximum level for revenue at 105% of target, a level that presents a significant challenge requiring exceptionally strong performance. The Compensation Committee set maximum levels for the other two metrics that were also based on our 2022 operating plan, including the planned growth in revenue and expenses, and that required significant effort to achieve.

Payout Levels

The Compensation Committee defined payout levels representing the amount to be paid to NEOs based on the level of actual performance relative to the targets. If achievement is below the threshold level of performance, the Compensation Committee set the payout at 0% in order to motivate performance and underscore the importance of achieving, or closely approaching, the targets at this critical time in our development. If we achieve threshold performance on a metric, the payout is 50% of target; if we achieve 100% of target performance, the payout is 100% of target, and if we achieve maximum performance, the payout is 200% of target. For performance between the threshold and maximum for any metric, the payout amount is interpolated as a payout percentage between a threshold of 50% and a maximum of 200%.

52

With respect to the Operational Performance Component, for the oncology products and performance, the launches of Guardant Reveal and Guardant360 were on target, while the new product reimbursement and new product clinical volume were between threshold and target. For the screening research and development performance, the ECLIPSE study read out and the LDT launch were on target, and the data presentation regarding Guardant SHIELD multi-cancer was above target.

With respect to the Financial Performance Component, as described above, total revenue increased to $449.5 million for the year ended December 31, 2022, a 20% increase from $373.7 million for the year ended December 31, 2021.

With respect to the employee retention metric, performance was nearly at target.

The following tables show (1) for each operational performance component and employee retention measure, the weighted payout, and (2) for each financial performance component, the achievements necessary to obtain payouts at the target level, the actual result for each performance component and the resulting achievement percentage, as well as the weighted payout:

53

Target Opportunities

The Compensation Committee determines the target cash incentive opportunity available to each NEO by taking the individual’s annual base salary in effect at year end and multiplying it by the individual’s target incentive percentage. Among other factors, the target incentive percentages are determined with reference to the peer group company percentages of salary and the proportion of total direct compensation represented by the annual incentive.

Payout Determination

The Compensation Committee verifies our achievement relative to the targets for the Operational Performance Component, Financial Performance Component and employee retention metric to determine the respective performance levels, and then translates those performance levels to a payout level based on linear interpolation between achievement levels. As noted above, for 2022, the payout level was 67%.

Having determined the total 2022 annual incentive plan payouts for each eligible NEO, the Compensation Committee then shared its conclusions with the Board for discussion.

Long-Term Incentives

The third and largest component of our executive compensation program is long-term equity incentives. The Compensation Committee has designed the long-term incentive opportunity for the NEOs to motivate and reward executive officers to achieve multi-year strategic goals and deliver sustained long-term value to stockholders, while at the same time monitoring the overall dilutive effect of equity granted.

The long-term incentives create a strong link between payouts and performance, and a strong alignment between the interests of executive officers and the interests of our

54

stockholders. Long-term equity incentives also promote retention, because executive officers will only receive value if they remain employed by us over the required term, and they foster an ownership culture among our executive officers by making executive officers become stockholders, with a personal stake in the value they are incentivized to create.

Equity Vehicles

For 2022, long-term incentive grants took the form of 50% stock options and 50% RSU awards. The Compensation Committee structures the mix of equity vehicles and the relative weight assigned to each type to motivate stock price appreciation over the long term through stock options, which deliver value only if the stock price increases, and to ensure value delivery through the RSUs, reinforcing an ownership culture and commitment to us.

The target mix of long-term incentives approved by the Compensation Committee for the NEOs in 2022 as annual equity grants is shown below. The number of RSUs and stock options subject to each award is determined pursuant to the terms of our Equity Award Guidelines, which was last approved by the Compensation Committee in November 2022.

2022 Annual Equity Grants

Typically, in making determinations about long-term equity incentive grants to the NEOs, the Compensation Committee considers equity grant levels and the overall pay mix in peer group companies and the NEO’s role, skills and experience and the critical nature of the NEO’s contributions to the Company, among other things. The grants to the NEOs vary based on these factors. This portion of the NEOs’ total direct compensation is variable and directly aligned with stockholder interests.

The Compensation Committee made no equity grants to the co-CEOs in 2022 pursuant to the terms of the Waiver Letters.

55

2022 Annual Equity Grants

2023 PSU Grants

In the first quarter of 2023, the Compensation Committee increased the performance nature of long-term incentives by granting performance stock units, or PSUs. The 2023 PSUs vest over a three-year performance period ending December 31, 2025 based on revenue and a three-year Compound Annual Growth Rate, or CAGR, each weighted 50%. The CAGR metric underscores the importance of consistent strong revenue growth over the 2023-25 performance period. The actual number of PSUs earned will be based on the Company’s performance relative to target. The addition of these PSUs reinforces the pay-for-performance nature of the long-term incentive grants and the executive compensation program overall.

The Compensation Committee views the use of these measures as critical because they tie executive officer compensation with key long-term priorities and align the interests of executive officers with those of Guardant and its shareholders. The performance-based metrics, in conjunction with the proportion of total compensation that was variable and at-risk, further enhance the link between pay and performance for the NEOs, as well as strengthened the alignment of the interests of the executive officers with those of our stockholders. The Compensation Committee intends, as appropriate and in line with the further development of the Company over time, to consider increasing the proportion of long-term incentives allocated to performance-based vehicles.

The Company maintains an ongoing commitment to good corporate governance principles and strong performance orientation in our compensation program by proactively reviewing our policies and program design. We continue to manage award amounts, with a goal of maintaining broad-based equity participation, delivering value that is aligned with our compensation philosophy and proactively managing our share usage as well as dilution during a period of rapid growth.

We expect to continue to evaluate our equity compensation strategy across the organization to manage our equity utilization during 2023 and beyond.

Promotion of John Saia to Chief Legal Officer

Effective April 3, 2022, the Board promoted John Saia to the position of Chief Legal Officer. In connection with Mr. Saia’s promotion, after considering the increase in scope to Mr. Saia’s role and responsibilities, as well as market data provided by our independent compensation consultant, internal equity, advice from our independent compensation consultant and other factors, the Compensation Committee made a one-time grant of 60,548

56

stock options and 30,274 RSUs to Mr. Saia in August 2022, with a target dollar-denominated value for such award of $3,000,000. The equity awards granted to Mr. Saia in connection with his promotion vest over four years.

Other Elements of Compensation

401(k) Plan

We currently maintain a 401(k) retirement savings plan for our employees, including our NEOs, who satisfy certain eligibility requirements. The 401(k) plan is intended to qualify as a tax-qualified plan under Section 401(k) of the Internal Revenue Code (the “Code”), and our NEOs are eligible to participate in the 401(k) plan on the same basis as our other employees. The Code allows eligible employees to defer a portion of their compensation, within prescribed limits, on a pre-tax basis through contributions to the 401(k) plan. We believe that providing a vehicle for tax-deferred retirement savings though our 401(k) plan adds to the overall desirability of our executive compensation package and further incentivizes our employees, including our NEOs, in accordance with our compensation policies. In 2022, we provided a discretionary contribution equal to 50% of the first 6% contributed by the employee.

Employee Benefits

All of our full-time employees, including our NEOs, are eligible to participate in our health and welfare plans, including:

We also provide supplemental short-term disability coverage to our NEOs in addition to the short-term disability coverage provided to our full-time employees generally.

We believe the benefits and limited perquisite described above are necessary and appropriate to provide a competitive compensation package to our named executive officers.

Severance Arrangements

We maintain the Guardant Health, Inc. Executive Severance Plan (the “Severance Plan”). The Severance Plan provides for the payment of certain severance and other benefits to participants. The Severance Plan generally provides for severance amounts if the NEO’s employment is terminated by us without cause or by the NEO for good reason. For terminations not in connection with a change in control, severance amounts range from 50% to 100% of base salary. For terminations from three months prior to one year after a change in control, severance amounts range from 100% to 150% of the sum of base salary and target cash bonus. The Severance Plan also provides for reimbursement for health benefit continuation of up to 18 months. The payments and benefits provided under the Severance Plan are contingent upon the affected NEO’s execution and non-revocation of a general release of claims and compliance with specified restrictive covenants. See “Potential

57

Payments upon a Termination or Change in Control,” which describes the payments to which the participating NEOs may be entitled under the Severance Plan.

In addition, in 2019, we entered into letter agreements with each of Drs. Eltoukhy and Talasaz that provide that if the executive experiences a “qualifying termination” of employment (as defined in the Severance Plan), other than in connection with a change in control, then each time-based vesting Company equity award held by the executive will vest and become exercisable as to the portion of the award that would have vested over the one-year period following the termination date (had the executive remained in continuous service during such period). This acceleration right is subject to the executive’s timely executive and non-revocation of a general release of claims.

V. ADDITIONAL COMPENSATION POLICIES AND PRACTICES

Stock Ownership Guidelines

To support our commitment to stockholder alignment and ensure non-employee members of our Board and our executive officers, including our NEOs, remain invested in our performance and the performance of our common stock, we adopted stock ownership guidelines effective January 2020, which were amended effective November 2022. Pursuant to the amended guidelines, we no longer include unexercised stock options in the definition of ownership for purposes of determining whether our NEOs have satisfied the stock ownership guidelines. We also increased the minimum ownership guidelines for our co-Chief Executive Officers to reflect a multiple of the current median salary of chief executive officers in our 2022 executive compensation peer group.

Our stock ownership guidelines require applicable individuals to hold a certain value of our common stock depending on their position with us, as follows:

Each individual subject to our stock ownership guidelines has until the later of January 1, 2026 or the fifth anniversary of his or her designation as being subject to the guidelines to comply with the stock ownership guidelines applicable to his or her position. Shares of common stock that count toward satisfaction of the ownership requirements include shares of common stock held directly or indirectly through certain trusts or entities, and outstanding RSUs that vest solely based on the passage of time. Shares underlying unexercised stock options and unearned performance-based stock awards do not count in determining compliance with the stock ownership guidelines.

Until a participant subject to our stock ownership guidelines meets the applicable minimum ownership guidelines, such participant is required to retain (and not dispose of or otherwise

58

transfer) 20% of all “net settled shares” received from the vesting, delivery and/or exercise of equity awards granted under the Company’s equity incentive plans for one year subsequent to their vesting, delivery and/or exercise. For purposes of the stock ownership guidelines, “net settled shares” means those shares of common stock that remain after payment of the applicable exercise or purchase price and all applicable withholding taxes and transaction costs.

Anti-Hedging and Anti-Pledging Policies

We maintain an Insider Trading Compliance Policy that prohibits our officers, directors and employees from purchasing financial instruments (including prepaid variable forward contracts, equity swaps, and collars), or otherwise engaging in transactions, that hedge or offset, or are designed to hedge or offset, any decrease in the market value of our stock. It further prohibits pledging our stock as collateral to secure loans, margin purchases of our stock, short sales of our stock, and any transactions in puts, calls or other derivative securities involving our stock.

Accounting Policies for Stock-Based Compensation

We follow the Financial Accounting Standards Board’s Accounting Standards Codification Topic 718, or ASC Topic 718, for our stock-based compensation awards. ASC Topic 718 requires companies to calculate the grant date “fair value” of their stock-based awards using a variety of assumptions. ASC Topic 718 also requires companies to recognize the compensation cost of their stock-based awards in their income statements over the period that an employee is required to render service in exchange for the award. Grants of stock options and restricted stock units under our equity incentive award plans are accounted for under ASC Topic 718. Our Board or Committee will consider the accounting implications of significant compensation decisions, especially in connection with decisions that relate to our equity incentive award plans and programs. As accounting standards change, the Compensation Committee may revise certain programs to appropriately align accounting expenses of equity awards with the overall executive compensation philosophy and objectives.

Report of the Compensation Committee on Executive Compensation

This Compensation Committee Report shall not be deemed to be incorporated by reference into any filing made by the Company under the Securities Act of 1933 or the Exchange Act, notwithstanding any general statement contained in any such filing incorporating this proxy statement by reference, except to the extent the Company incorporates such Report by specific reference.

The Compensation Committee has reviewed and discussed the Compensation Discussion and Analysis with the management of the Company. Based on this review and these discussions, we have recommended to the Board of Directors that the Compensation Discussion and Analysis be included in the Company’s Annual Report on Form 10-K and the Company’s proxy statement.

The preceding report has been furnished by the following members of the Compensation Committee:

Vijaya Gadde, Chair

Samir Kaul

Myrtle Potter

59

COMPENSATION TABLES

Summary Compensation Table

60

2022 Grants of Plan Based Awards Table