Injection drug users constitute 60% of the more than 4 million people in the United States with hepatitis C virus (HCV), including many methadone maintenance patients. Few data exist describing clinical outcomes for patients receiving HCV treatment on-site in methadone maintenance settings. In this retrospective study, we describe clinical outcomes for 73 patients receiving HCV treatment on-site in a methadone maintenance treatment program. Fifty-five percent of patients achieved end-of-treatment response, and 45% achieved sustained viral response. These treatment response rates are nearly equivalent to previously published HCV treatment response rates, despite high prevalences of ongoing drug use (49%), psychiatric comorbidity (67%), and HIV coinfection (32%). These data show that on-site HCV treatment with pegylated interferon and ribavirin is effective in methadone-maintained patients, many of whom are active drug users, psychiatrically ill, or HIV coinfected, and that methadone maintenance treatment programs represent an opportunity to safely treat chronic hepatitis C.