The first aim of this study was to investigate the recreational use of nitrous oxide (N2O) among health profession students at Montpellier University (France). The second aim was to identify the factors associated with N2O use. All students in medicine, dentistry, pharmacy and midwifery of the Montpellier University were contacted by email to participate in the survey. The students answered directly online by filling out anonymously a questionnaire including demographic information and questions about N2O, illicit drugs and alcohol use. Ethical approval was granted by the ethics committee of the Montpellier University. The sample comprised 593 students (mean age = 22.3 ± 2.6 yr), with 68.6% of females. Lifetime N2O use was reported by 76.6% and frequent alcohol use by 30.5% of the respondents. The lifetime use of cannabis, ‘poppers’, cocaine, ecstasy and LSD was 26.8%, 54.6%, 9.6%, 10.1% and 2.0% respectively. In multivariate analysis, the substances significantly associated with lifetime N2O were alcohol drinking and ‘poppers’ use. With respect to this self-nominated sample, our results indicate that respondents who were alcohol drinkers, were poppers users, follow longer studies, divert medical products for recreational use or were members of a students’ corporation had higher odds of lifetime N2O use.