The prevalence of HIV has been rising among injection drug users (IDUs) and AIDS is now an important cause of death among that population. We tracked mortality and recorded detailed causes of death in the Vancouver Injection Drug Users Study (VIDUS). This is an open cohort of over 1,400 active IDUs that began in May 1996. At enrollment and at semiannual follow-up visits, a trained interviewer administers a detailed semistructured questionnaire. Mortality was recorded during follow-up and detailed causes of death were collected from coroner's reports, hospital records, and the provincial (British Columbia) registry. Causes of death were obtained on 125 participants. Overall, the leading cause of death was overdose accounting for 25% of deaths among HIV-positive participants and 42% among HIV-negative participants. Of the 65 deaths among HIV-positive individuals, 22 (34%) were HIV related. Mortality was associated with older age (adjusted hazards ratio [AHR], 1.03 per year), HIV positivity (AHR, 2.67), injection cocaine use (AHR, 2.23) and methadone treatment (AHR, 0.47). The high rate of HIV in this population has added significantly to the burden of illness and death in this marginalized population.