BACKGROUND. In studies of hepatitis C virus (HCV) seroconversion in injection drug users (IDUs), some have questioned whether underreporting of syringe sharing, a stigmatized behavior, has led to misattribution of HCV risk to other injection-related behaviors. METHODS. IDUs aged 15-30 years who were seronegative for human immunodeficiency virus and HCV antibodies were recruited into a prospective study in 5 US cities. Behavioral data were collected via computer-assisted self-interviewing to reduce socially desirable reporting. Hazard ratios (HRs) were estimated to assess associations between behavior and HCV seroconversion. Because the shared use of cookers, cottons, and rinse water was highly correlated, a summary variable was created to represent drug preparation equipment sharing. RESULTS. Among 483 IDUs who injected during the period covered by the follow-up assessments, the incidence of HCV infection was 17.2 cases per 100 person years; no HIV seroconversions occurred. Adjusting for confounders, the shared use of drug preparation equipment was significantly associated with HCV seroconversion (adjusted HR, 2.66; 95% confidence interval, 1.03-23.92), but syringe sharing was not (adjusted HR, 0.91). We estimated that 37% of HCV seroconversions in IDUs were due to the sharing of drug preparation equipment. CONCLUSIONS. Associations between sharing drug preparation equipment and HCV seroconversion are not attributable to underascertainment of syringe sharing. Avoiding HCV infection will require substantial reductions in exposure to all sources of contaminated blood.