Brazil has recently integrated HIV Pre-exposure Prophylaxis (PrEP) into its public health system and offered to key populations such as transgender women (TGW). This study investigates factors associated with PrEP refusal among TGW living in one of the largest and poorest cities of Brazil. We recruited 127 TGW using Respondent Driven Sampling (RDS) in Salvador, Brazil. Latent class analysis (LCA) was used to define acceptability of PrEP. Two latent classes were identified: “high acceptability of PrEP” (91.3%) and “PrEP refusal” (8.7%). PrEP was less acceptable among white TGW and among those age 25 or older, with income above minimum wage (≥ US$252.87), and reporting unprotected receptive anal intercourse with (URAI) causal partners. The findings highlight how nuanced strategies that takes into consideration unique characteristics are needed to effectively address the acceptability of PrEP.