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(1) Background: To evaluate the epidemiological profile of people who use drugs at the PrEP outpatient clinic of the University Hospital of Brasília; (2) Methods: Cross-sectional study with a review of data from medical records referring to the first medical consultation. The prevalence ratio was calculated using a Poisson regression model with robust variance; (3) Results: A total of 53% of subjects reported drug use in the last 3 months. The unadjusted prevalence ratio of drug use in trans women was PR: 9.0 (95%CI: 1.4–57.5). people who use drugs have a 1.9 times higher prevalence of STI diagnosis, and a 2.4 times higher prevalence of partners compared to non-users; (4) Conclusions: Substance use was associated with a higher STI prevalence ratio and number of sexual partners.