Background: Human immunodeficiency virus (HIV) remains prevalent in the United States despite medications that reduce the risk of infection, primarily pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP). In 2019, California authorized pharmacists to furnish PrEP and PEP under Senate Bill 159 (SB-159). Objective: Assess implementation of SB159 in San Francisco Bay Area community and mailorder pharmacies. Methods: We conducted an observational, cross-sectional survey of independent community and mail-order pharmacies in the 9-county San Francisco Bay Area to identify those that were in the process of furnishing, actively furnished, or furnished under a collaborative practice agreement (CPA). We conducted interviews with furnishing pharmacies in April 2021, focusing on the barriers to and successes of implementation, as well as the impact of coronavirus disease 2019 (COVID-19), and qualitatively analyzed them. Results: Of the 209 pharmacies contacted, 6 furnished under SB-159 (2.9%), 2 were in the process of furnishing under SB-159, and 1 furnished under a CPA. Six pharmacies and 7 pharmacists were interviewed. Barriers to implementation and furnishing included COVID-19, laboratory tests, lack of time and staff, cost to pharmacy, refill limitation, lack of patient awareness, difficulty arranging follow-up care, and vague wording of the policy. Facilitators to implementation included collaborations with clinics and health centers, privacy, increased accessibility, increased need in the patient population, and the pharmacy culture. Conclusion: Barriers and facilitators to PrEP and PEP furnishing were consistent across pharmacies, suggesting strategies that could be replicated and potential improvements to SB-159.