OBJECTIVE The prevalence of HIV among psychiatric patients is higher than general population rates worldwide. Many risk behaviors have been identified in studies from both developing and developed countries, though sampling limitations restrict the generalizability of their results. The objective of this study was to report findings from the first national sample of psychiatric patients about lifetime practice of unsafe sex and associated factors. METHODS A national multicenter sample of adults with mental illness was randomly selected from 26 public mental health institutions throughout Brazil. Sociodemographic, sexual behavior and clinical data were obtained from person-to-person interviews and blood was collected for serology testing. Logistic regression was used for analysis. RESULTS The overall prevalence of lifetime unprotected sex was 80.3%. Married, older, female patients, those with multiple partners and living with children or partners only and those with less severe psychiatric diagnosis more often practised unsafe sex. CONCLUSIONS Risk behavior assessment is a critical tool for clinicians to be able to determine needed HIV-related services for their clients and ensure appropriate follow-through with care and prevention. Interventions that address situational risks in psychiatric patients' lives-institutional and individual- and increase their ability to make informed decisions about their sexual health are urgently needed.