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Background Illicit substance use among college students represents one of the most complicated social problems. Studying its predictors could help deal with this problem more efficiently. Aims To determine the prevalence of life time illicit substance use and its predictors among Tunisian college students. Methods A cross-sectional study was conducted in five colleges in the region of Sousse, Tunisia in the 2012-2013 school year. A sample of 556 college students responded to an anonymous self-administrated questionnaire. Collected data concerned socio-demographic characteristics and substances use. Results The mean age of students was 21.8 ± 2.2 years. Females represented 51.8% of participants. Among respondents: 31 (5.6%) had used illicit substance at least once. Cannabis was the main substance used by 26 (4.7%) students. The average age of the illicit substance use initiation was 19 (±2.5) years while it was almost 17 (±3) years for both tobacco and alcohol use initiations. Proportions of male students and academic failure were significantly more important among illicit substance users than among non users. While the most influential factors on illicit substance use were: alcohol use, tobacco use and low socioeconomic level. Conclusion This study highlights the strong association between the other risk behaviors and illicit drug use. Future interventions should focus on the whole risk behaviors simultaneously at late adolescence with regard to the environmental context.

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