Objective: To describe the use of psychoactive substances during sexual intercourse and associated risk factors. Materials and methods: In 2015, an anonymous self-administered questionnaire was offered on a voluntary basis to all patients visiting four HIV and viral hepatitis screening and follow-up centers in the Alpes-Maritimes region during a one-week period. This questionnaire collected data on psychoactive substance use, methods of administration, use during sexual intercourse, and associated sexual risk-taking. Results: Among the 472 patients seen, 306 provided usable questionnaire responses; 110 (36%) of them had used psychoactive substances in the previous month, including 50 (16%) during sexual intercourse. Among the latter, 88% were men, with a median age of 34 years, and they were predominantly gay or bisexual (56%). Patients reported HIV-positive status in 44% of cases and HCV-positive status in 8%. Risky patterns of psychoactive substance use were reported by 86% of individuals, substance use combined with alcohol by 70%, and the use of at least three substances by 68%. The main associated sexual risks were: having more than one partner in the past month (56%), not using condoms (50%), or engaging in group sex (28%). In multivariate analysis, risk factors for psychoactive substance use during sexual intercourse were homosexuality/bisexuality (OR: 6.17 [2.23–19.62], p=0.001) and the use of stimulants/amphetamines (OR: 9.02 [3.23–29.24], p<0.001). Self-reported HIV seropositivity was not associated with the use of psychoactive substances during sexual intercourse. Conclusion: Our results should help tailor health education strategies for this population by combining sexual risk reduction with risk reduction related to psychoactive substance use.