Abstract: Background: Many intravenous opiate users are infected with hepatitis C virus (HCV) but few are treated. Although this complies with various guidelines, virtually no published evidence supports such a recommendation. Patients and Methods: In a multicenter study, HCV-infected patients in opiate maintenance treatment programs received interferon plus high- or low-dose ribavirin (1000/1200 mg or 600 mg). HIV-coinfected patients were not included. Endpoints were feasibility, efficacy, side effects, and reasons for dropout. Results: Of the 420 patients who tested positive for HCV, 27 (6%) were enrolled; 393 (94%) either failed to meet the inclusion criteria or refused treatment. Virologic end-of-treatment response was achieved in 12/27 patients, and sustained response in 13/27 (48%). Response depended on viral genotype, not ribavirin dose. The two doses of ribavirin did not differ in their side effects. Conclusion: In a small fraction of HCV-infected intravenous drug users in an opiate maintenance treatment program, antiviral therapy was feasible, safe and effective. The success rate was comparable to that achieved in controlled studies that excluded drug users.