To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response.

Prospective cohort recruited between 2009 and 2012. Participants were treated with peg‐interferon alfa‐2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1).

Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community‐controlled health organization providing drug treatment services in New South Wales, Australia.

Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female).

Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA >24 weeks post‐treatment).

Among 101 treated, 37% (n = 37) had recently injected drugs (past 6 months) and 62% (n = 63) were receiving OST. Adherence ≥ 80% was 86% (n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age < 35 (versus ≥ 45 years) [adjusted odds ratio (aOR) = 5.06, 95% confidence interval (CI) = 1.47, 17.40] and on‐treatment adherence ≥ 80% independently predicted SVR (aOR = 19.41, 95% CI = 3.61, 104.26]. Recent injecting drug use at baseline was not associated with SVR.

People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon‐based therapy similar to other populations, despite injecting drugs at baseline. Younger age and adherence are predictive of improved response to hepatitis C virus therapy.