OBJECTIVE To examine the relationship between non-fatal overdose and risk of subsequent fatal overdose. METHODS We assessed risk factors for overdose death among two prospective cohorts of persons who inject drugs (PWID) in Vancouver, Canada. Extended Cox regression was used to examine if reports of non-fatal overdose were associated with the time to fatal overdose while adjusting for other behavioral, social and structural confounders. RESULTS Between May, 1996 and December, 2011, 2317 individuals were followed for a median of 60.8 months. In total, 134 fatal overdose deaths were identified for an incidence density of 8.94 (95% confidence interval [CI]: 7.55-10.59) deaths per 1000 person-years. During the study period there were 1795 reports of non-fatal overdose. In a multivariate model, recent non-fatal overdose was independently associated with the time to overdose mortality (adjusted hazard ratio [AHR]=1.95; 95% CI: 1.17-3.27). As well, there was a dose response effect of increasing cumulative reports of non-fatal overdose on subsequent fatal overdose. CONCLUSIONS Reports of recent non-fatal overdose were independently associated with subsequent overdose mortality in a dose-response relationship. These findings suggest that individuals reporting recent non-fatal overdose should be engaged with intensive overdose prevention interventions.