The frequent conflation of transgender ('trans') women with 'men who have sex with men (MSM)' in HIV prevention obscures trans women's unique gender identities, social and behavioural vulnerabilities, and their disproportionately high rates of HIV infection. Pre-exposure prophylaxis (PrEP) is an efficacious biomedical HIV prevention approach. However, trans women are underrepresented in PrEP research, and are often aggregated with MSM without consideration for their unique positions within sociocultural contexts. This study examined PrEP acceptability among trans women via three focus groups and nine individual interviews (total N = 30) in San Francisco. While knowledge of PrEP was low, interest was relatively high once participants were informed. Due to past negative healthcare experiences, ability to obtain PrEP from a trans-competent provider was cited as essential to PrEP uptake and adherence. Participants noted that PrEP could address situations in which trans women experience reduced power to negotiate safer sex, including sex work. Trans-specific barriers included lack of trans-inclusive marketing of PrEP, prioritisation of hormone use, and medical mistrust due to transphobia. Findings underscore the importance of disaggregating trans women from MSM in HIV prevention strategies to mitigate disparate risk among this highly vulnerable population.