To examine rates and predictors of referral for hepatitis C virus (HCV) treatment and preliminary treatment outcomes in injecting drug users (IDUs) receiving opioid replacement treatment, a prospective clinical audit was undertaken in an inner city Sydney drug dependency treatment practice between December 2002 and November 2005. The majority of IDUs (178/237; 75%) were HCV antibody positive, of whom 170 were HCV treatment naïve with no absolute treatment contraindications. Among these 170 patients, 121 (71%) had chronic HCV. Based on risk factors for HCV disease progression, 63 of 121 (52%) chronic HCV patients were targeted for referral; these patients were older, had higher alanine aminotransferase levels and longer estimated duration of HCV infection. Of these 63 patients, 43 were referred to a hepatitis treatment clinic, and 27 attended during the audit period. Patients who attended for treatment assessment were more likely to have genotype 2 or 3 (p<0.001), but socio-behavioural factors were similar. Liver biopsy was performed in 20 patients, with moderate or greater fibrosis in 18 patients. Of 14 patients commenced on pegylated interferon-alpha and ribavirin therapy, one ceased treatment due to non-response, 10 have completed treatment, all with an end-of-treatment (n=4) or sustained virological response (n=6), and treatment is ongoing in three. The development of HCV treatment referral criteria has allowed prioritisation of patients for referral, potentially halving those that require early assessment. Preliminary HCV treatment outcomes are encouraging and highlight the potential for reducing liver disease burden in this patient population.