The aim of this study was to measure the impact of hepatitis C virus (HCV) infection on mortality in a cohort of inner city residents. The Community Health and Safety Evaluation is a community-based study of inner city residents followed retrospectively and prospectively through linkages with provincial virology and mortality databases. We identified participants having received HCV antibody testing, evaluated cause-specific mortality rates and factors associated with all-cause and liver-related mortality using Cox Proportional Hazards models. Overall, 2332 participants received HCV antibody testing (recent non-injection drug use - 81%). The prevalence of HCV and HIV was 64% (1495 of 2332) and 21% (485 of 2332), respectively. Between January 2003 and December 2007, there were 180 deaths (192 per 10.000 person-years; 95% CI: 165, 222), with 21% HIV-related, 20% drug-related and 7% liver-related. Mortality was associated with age >50 [adjusted hazard ratio (AHR) 2.80 vs 50 [AHR 18.49 vs 50 years of age were at significant risk of liver-related mortality. Continued surveillance of this population infected with HCV in the 1970s and 1980s is important.