BACKGROUND Non-fatal drug overdose is a major cause of morbidity among people who use drugs, although few studies have examined this risk among street-involved youth. We sought to determine the risk factors associated with non-fatal overdose among Canadian street-involved youth who reported illicit drug use. METHODS Using data from a prospective cohort of street-involved youth in Vancouver, Canada, we identified youth without a history of overdose and employed Cox regression analyses to determine factors associated with time to non-fatal overdose between September 2005 and May 2012. RESULTS Among 615 participants, 98 (15.9%) reported a non-fatal overdose event during follow-up, resulting in an incidence density of 7.67 cases per 100 person-years. In multivariate Cox regression analyses, binge drug use (adjusted hazard ratio [AHR]=1.85; 95% confidence interval [CI]=1.20-2.84), non-injection crystal methamphetamine use (AHR=1.70; 95% CI=1.12-2.58), non-injection prescription opiate use (AHR=2.56; 95% CI=1.36-4.82), injection prescription opiate use (AHR=2.49; 95% CI=1.40-4.45) and injection heroin use (AHR=1.85; 95% CI=1.14-3.00) were positively associated with time to non-fatal overdose. Social, behavioural and demographic factors were not significantly associated with time to non-fatal overdose event. CONCLUSIONS Rates of non-fatal overdose were high among street-involved youth. Drug use patterns, in particular prescription opiate use, were associated with overdose. These findings underscore the importance of addiction treatment and prevention efforts aimed at reducing the risk of overdose among youth.