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The HIV epidemic affects men who have sex with men (MSM) disproportionally in Brazil, and pre-exposure prophylaxis (PrEP) is effective for preventing HIV in this population. However, low perceived risk of HIV may influence the acceptability and decision to use PrEP. This study estimated the association between self-perception of HIV risk and acceptability of daily oral PrEP among Brazilian MSM. Respondent-driven sampling (RDS) was used for behavioral and biological surveillance to recruit 4,176 MSM 18 years or over in 12 Brazilian cities in 2016. Results were weighted using Gile's estimator in RDS Analyst software. Adjusted odds rations (OR) with 95% confidence intervals were calculated using multivariate logistic regression. Acceptability of daily oral PrEP was high (69.7%) among the 3,544 MSM available for analysis. Most participants self-reported low or moderate risk of HIV infection (67.2%) and a small proportion (9.3%) reported high risk. A dose–response relationship was observed between acceptability of PrEP and self-reported risk: PrEP acceptability was 1.88 times higher (OR 1.8; 95% CI: 1.24–2.85) among MSM whose perceived risk of HIV infection was low or moderate, and 5 times higher (OR 5.68; 95% CI: 2.54–12.73) among those who self-reported high risk compared to MSM reporting no HIV risk. MSM with the highest risk perception of HIV reported higher rates of PrEP acceptability. Given the availability of daily oral PrEP in the public health care system in Brazil, we suggest emphasizing counseling about self-perception of HIV risk as part of routine HIV prevention services. [ABSTRACT FROM AUTHOR]