Access to hepatitis C virus (HCV) treatment remains extremely limited among people who inject drugs (PWID). HCV assessment and treatment was evaluated through an innovative model for the provision of HCV care among PWID with chronic HCV infection. Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) was a prospective observational cohort. Recruitment was through 5 opioid substitution treatment (OST) clinics, 2 community health centers, and 1 Aboriginal community controlled health organization in New South Wales, Australia. Among 387 enrolled participants, mean age was 41 years, 71% were male, and 15% were of Aboriginal ethnicity. Specialist assessment was undertaken in 191 (49%) participants, and 84 (22%) commenced interferon-based treatment. In adjusted analysis, HCV specialist assessment was associated with non-Aboriginal ethnicity (adjusted odds ratio [AOR], 4.02; 95% confidence interval [CI], 2.05-7.90), no recent benzodiazepine use (AOR, 2.06; 95% CI, 1.31-3.24), and non-1 HCV genotype (AOR, 2.13; 95% CI, 1.32-3.43). In adjusted analysis, HCV treatment was associated with non-Aboriginal ethnicity (AOR, 4.59; 95% CI, 1.49-14.12), living with the support of family and/or friends (AOR, 2.15; 95% CI, 1.25-3.71), never receiving OST (AOR, 4.40; 95% CI, 2.27-8.54), no recent methamphetamine use (AOR, 2.26; 95% CI, 1.12-4.57), and non-1 HCV genotype (AOR, 3.07; 95% CI, 1.67-5.64). HCV treatment uptake was relatively high among this highly marginalized population of PWID. Potentially modifiable factors associated with treatment include drug use and social support.