Background: Chemsex-the use of psychoactive substances during sexual encounters-among men who have sex with men is a growing concern. On-demand HIV pre-exposure prophylaxis (PrEP) may be a suitable tool to prevent HIV transmission among "chemsexers." We used the open-label extension study of the ANRS-IPERGAY trial to describe chemsexers and their PrEP use. Methods: Among the 361 men who have sex with men enrolled in ANRS-IPERGAY's open-label extension study, we selected the 331 with available data on drug use. A 2-monthly web questionnaire on sociobehavioral data was used to compare sexual behaviors between questionnaires where chemsex was reported and those where it was not. Using a generalized estimating equation logistic regression, we studied whether practicing chemsex was associated with correct PrEP use. Results: Among the 331 participants, 30% reported chemsex practice at least once during follow-up and were considered chemsexers. Chemsex was reported in 16% of all questionnaires. Chemsexers were not significantly different from nonchemsexers regarding sociodemographic characteristics, although they reported greater use of anxiolytics and more sensation-seeking. Reporting chemsex was associated with more high-risk sexual practices and a higher perception of risk. After adjustment for other potential correlates, chemsex remained associated with correct PrEP use [odds ratio (95% confidence interval) = 2.24 (1.37 to 3.66)]. Conclusions: Our findings show that chemsexers were more likely to report high-risk sexual practices but also had a higher perception of risk. They were also more likely to use PrEP correctly when practicing chemsex. Consequently, PrEP may be a suitable tool to reduce HIV-risk transmission among chemsexers.