Through community-based outreach, young adult injection drug users (IDUs) were enrolled in a prospective study of the prevalence, incidence, and risk factors for hepatitis C virus (HCV) infection. Demographics and information on sexual and injecting practices were collected during semiannual interviews, and HCV infection was evaluated using a second-generation antibody assay. Of the 229 participants, 86 (37.6%) were HCV-seropositive at baseline. After adjusting for injecting frequency and duration by logistic regression, HCV seroprevalence was independently associated with reusing syringes at least once in the past 6 months (odds ratio [OR]=3.81, 95% confidence interval [CI] 1.39-11.00), injecting the first time with someone > or =5 years older (OR=2.99; 95% CI, 1.43-6.23) or alone (OR=4.02; 95% CI, 1.12-14.43) versus with someone <5 years older, and injecting cocaine or speedball exclusively (OR=4.29; 95% CI, 1.53-12.01) or with other drugs (OR=5.27; 95% CI, 2.62-10.64) versus injecting no cocaine in the past 6 months. Of the 105 originally HCV-seronegative participants who returned for follow-up, 13 seroconverted (incidence rate=16.0/100 person-years). On bivariate analysis, HCV seroconversion was significantly associated with injecting for <2 years (relative risk [RR]=7.3; 95% CI, 1.6-32.8) and continuing to inject during follow-up (RR=4.4; 95% CI, 1.0-19.9). Young adult IDUs are at high risk for HCV infection. These data support the need for wider legal access to sterile syringes, as well as expanded community outreach education to this population to prevent transmission of HCV.