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In a nationwide sample of cisgender Black women in the US, we assessed the associations between social and structural factors and interest in using HIV preexposure prophylaxis (PrEP). Among 315 respondents, 62.2% were interested in PrEP if it were provided for free. Positive social norms surrounding PrEP, including injunctive norms (perceived social acceptability of PrEP use) and descriptive norms (perceived commonality of PrEP use), were positively associated with interest in using PrEP. Concerns about HIV infection, recently visiting a health care provider, and comfort discussing PrEP with a provider were also positively associated with interest in using PrEP. Anticipating PrEP disapproval from others was negatively associated with interest in PrEP. Although PrEP can promote autonomy and personal discretion, Black women's PrEP-related decisions occur in a complex social environment. Black women may benefit from interventions to promote positive norms and attitudes surrounding PrEP at the community level and empower them in discussions with their providers about PrEP.