Among 559 street youth recruited between 2005 and 2007 in Vancouver, Canada, young drug users (<21 years of age) were compared with older drug users (≥21 years) with regard to recent drug use and sexual practices using multiple logistic regression. Older youth were more likely to be male and of Aboriginal ancestry, to have more significant depressive symptoms, to have recently engaged in crack smoking, and to have had a recent history of injection drug use. Young drug users, by contrast, were more likely to have engaged in recent binge alcohol use. Efforts to reduce drug use-related harm among street youth may be improved by considering the highly prevalent use of "harder" drugs and risk for depression among older youth.