Background- Current prescribing practices rely on a combination of evidence-based medicine (population-based drug response data from clinical trials and meta-analysis), trial-and-error approaches, practical experience, and clinical observation. Pharmacogenomics (PGx), the study of how genes affect the body’s response to specific medications,1 can help providers personalize drug prescriptions by providing guidance on dose, side effects, and efficacy based on genetic variations. PGx testing provides key information on potential drug-gene interactions that can be leveraged to optimize drug effectiveness while limiting side effects. Methods- PGx testing was implemented at the VA in 2019 through the National Pharmacogenomics Program (NPP), which aims to perform PGx testing on 250,000 Veterans. The PGx testing panel provides information on 11 different pharmacogenes and over 40 commonly prescribed medications used for cardiovascular conditions, mental health, pain management, inflammation, and cancer therapy. The NPP team provided standardized implementation templates and funding for project coordinators to launch PGx testing programs at local VA sites.2 An initial Plan-Do-Study-Act cycle informed implementation resources and processes that were utilized at site initiation, such as guiding the local site champions in forming onsite steering committees that engaged key stakeholders.3 Essential engagement strategies entail developing stakeholder interrelationships and educating the providers on PGx. A PGx result outlines gene phenotypes, lists medications affected by drug-gene interactions, and includes recommendations to providers based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Any potential actionable drug-gene pairs are entered in the electronic health records as structured data that feed into a Clinical Reminder Order Check (CROC) system, which provides real-time clinical decision support of medications potentially affected by pharmacogenes. Current State- Currently, 76 VA medical centers are participating in the VA NPP with a goal of providing access to PGx to >120 VAs in 2024. Since 2019, there had been over 39,000 PGx orders from 4,100 providers across various specialties. Over 14,000 CROC alerts have fired, two-thirds of which have resulted in modification of medications.4 Future State- As the NPP transitions PGx testing to sustainability phase, it will expand several initiatives. Through the Expanding Clinical Pharmacist Practitioners in Pharmacogenomics (EXCLAIM) program, a local pharmacist will provide PGx-specific support to providers onsite. The TelePGx program will facilitate remote pharmacist support for direct patient care and population health management. The NPP will explore PGx testing options within the VA or contract with outside labs. PGx informatics will move towards a single, centralized repository of PGx data which will collect all historical data from lab vendors and make such data accessible for clinical decision support. Furthermore, the NPP will implement national level clinical workflows which will target specific patient populations where PGx testing is most likely to prevent adverse drug events. Initial examples include patients undergoing coronary stenting, patients with depression, and patients treated with select chemotherapies. Key Learnings- Pharmacogenomics is an emerging, highly actionable precision medicine approach. The program has developed a roadmap to maximize uptake and optimize the use of PGx to improve drug response outcomes. Further program growth will require elevating provider awareness and education about pharmacogenomics.