The San Francisco Vaccine and Prevention Unit (SFVPU) provides scientific leadership, capacity to recruit study volunteers into vaccine and non-vaccine prevention trials, innovative methods for community engagement in research, and mentorship of junior investigators. We will test vaccine and prevention strategies likely to have the greatest impact in reducing HIV infection in the United States and globally through our affiliation with the HIV Vaccine Trials Network and the HIV Prevention Trials Network. The SFVPU is housed in the San Francisco Department of Public Health, using a non-profit fiscal pass-through agency, Public Health Foundation Enterprises, to provide fiscal and human-resource management.