The purpose of this study was to determine the correlation between the prevalence of hepatitis C virus (HCV) infection with duration of drug use and other risk factors among drug users. This survey covered 899 male drug users from Kaohsiung Narcotic Abstention Institute and Kaohsiung prison. The prevalence of positive anti-HCV was 67.2% among intravenous drug users (IVDU) and 14.7% among non-intravenous drug users (non-IVDU). Among intravenous (IV) drug users, age and duration of drug use were independently related to HCV seropositivity. Seroprevalence rate for HCV in the IVDU group increased with increasing duration of injection use within the first seven years of drug use. However, the steepest trajectory in seroprevalence of HCV infection occurred within the first four months. Due to the high rate of HCV infection among drug users, investigation of risk behaviors should be routine in such a group. A high frequency of HCV infection was also found among short-term injectors, which indicated that early risk reduction intervention was an important measure in moderating HCV infection.