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Emtricitabine/tenofovir disoproxil fumarate as pre-exposure prophylaxis (PrEP) can prevent HIV infection among at-risk individuals, including young transgender women (YTW). We used baseline data from 230 HIV-uninfected YTW (ages 16–29 years) who were enrolled in Project LifeSkills during 2012–2015. We examined factors associated with perceived acceptability of PrEP use (mean score = 23.4, range 10.0–30.0). Participants were largely transgender women of color (67%) and had a mean age of 23 years (SD = 3.5). In an adjusted multiple linear regression model, PrEP interest (β = 3.7, 95% CI 2.2–5.2) and having a medical provider who meets their health needs (β = 2.9, 95% CI 1.3–4.4) was associated with higher PrEP acceptability scores, whereas younger age (21–25 vs 26–29 years) (β = –2.0, 95% CI − 3.6 to − 0.4) and reporting transactional sex in the past 4 months (β = − 1.5 …