We performed a cross-sectional analysis of factors associated with diabetes mellitus among 557 drug users who were recruited from a methadone treatment program and were participating in a longitudinal study of hepatitis C virus (HCV) infection. We found that HCV infection was strongly associated with diabetes mellitus (adjusted odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.4) after controlling for age, race, unemployment, and body mass index. Among HIV-infected drug users, receipt of antiretroviral therapy (ART) for >1 year was also associated with diabetes (adjusted OR for receipt of ART without a protease inhibitor, 4.1 [95% CI, 1.1-15.5]; adjusted OR for receipt of ART including a protease inhibitor, 5.5 [95% CI, 1.5-20.4]).