Immigrant adolescents and adolescents born of immigrant parents are at increased risk of substance use which has been linked to difficulties in acculturation processes. However very few studies have examined the role of the different acculturation strategies and none of them have controlled for relevant psychopathological and socio-familial factors. The aim of this study was to investigate the role of acculturation in cannabis use in a sample of adolescents born of immigrant parents taking into account potential confounding variables. A sample of 292 high school students born in France from at least one foreign parent completed a questionnaire assessing cannabis use, acculturation orientations, ethnic identity and the most relevant potential confounders (depressive symptoms, sensation seeking, borderline and psychopathic traits, alcohol and tobacco use, parental attachment, life events, socioeconomic status and academic achievement). A regression analysis showed that acculturation orientations and ethnic identity explained a significant part of the variance in the frequency of cannabis use. Individualism, integration and assimilation were negatively associated with the frequency of cannabis use suggesting they might serve as protective factors.