The purpose of this study is to explore perceived barriers and facilitators to the uptake of future U.S. Food and Drug Administration-approved HIV vaccines among women at elevated risk for HIV. We conducted four client focus groups (N = 41) and one focus group of women's health care professionals (N =9). Participants were recruited from diverse community agencies and health care clinics in Los Angeles using purposive, venue-based sampling. Data were analyzed using narrative thematic analysis and Ethnograph qualitative software. Barriers to HIV vaccine uptake included fear of vaccine-induced HIV infection, reproductive side effects, injection concerns, gendered roles and power dynamics, HIV stigma, discrimination, affordability, and mistrust. The provision of affordable and accessible HIV vaccines, ideally through routine care, along with culturally tailored, gender-specific HIV vaccine intervention and policy, can ensure the full potential of HIV vaccines to empower women to protect themselves against HIV infection.