Background: Little is known about the levels of psychoactive substance use among college students, largely due to the lack of a national survey sample. In France, little attention has been paid to studies highlighting gender-specific differences in drug use. Methods: The 2005 Health Barometer, a representative telephone survey of the general population (ages 12–75, n = 30,514), included 1,290 college students, 1,480 employed individuals, and 538 unemployed individuals, all aged 18 to 25. For each gender, these three groups were compared using multivariate logistic regressions on various forms of legal and illegal drug use. These results and those from the 2000 wave of the Health Barometer were put into perspective. Results: The analysis shows that among women, alcohol and cannabis use, as well as episodes of drunkenness, are more frequent among unemployed women and female students than among employed women. Among men, these uses, as well as those of other illicit substances, are more frequent among unemployed men. Consequently, gender differences in alcohol and cannabis use are smaller among students than among employed or unemployed adults. For both genders, age-adjusted logistic models show that alcohol and tobacco use are less common among students, unlike cannabis use and alcohol intoxication. For most forms of use, gender differences are smaller among students. With the exception of the results observed for alcohol and tobacco, all these differences become insignificant when controlling for other sociodemographic variables. Compared to the 2000 data, students’ consumption patterns are somewhat less oriented toward alcohol intoxication and cannabis use. Conclusion: Students differ from employed adults in that they consume less alcohol and tobacco, but experience intoxication slightly more frequently. Cannabis use is similar. Unemployment is a risk factor for both genders, but pursuing higher education is associated with excessive alcohol and cannabis use among women, whereas this is not the case among men. [author’s abstract]