OBJECTIVES: Psychiatric and substance use disorders are common in hepatitis C patients and represent barriers to antiviral treatment. We evaluated the effect of integrating psychiatric and medical care on evaluation for and initiation of antiviral treatment in a cohort of 184 patients with chronic hepatitis C. METHODS: Integrated care consisted of screening for psychiatric problems with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), Beck Depression Inventory (BDI), Urine Drug Screen (UDS), and Primary Care Posttraumatic Stress Disorder (PC-PTSD) screens, referral based on specified cutoff scores to an established mental health (MH) provider, to a colocated psychiatric clinical nurse specialist (PCNS), or both. Data were collected retrospectively by chart review. RESULTS: Most patients (149/184, 81.0%) had at least one positive screen, 25.5% had a positive UDS. Among patients with positive screens, 38.3% had established MH providers, 47.0% had no MH provider and were referred to the PCNS, and 15.0% refused any psychiatric referral. Patients receiving integrated care with a colocated PCNS were significantly more likely to complete evaluation for and start antiviral treatment than other patients with positive screens, and at a rate similar to that of patients with negative screens. Patients with positive screens followed by any MH provider had significantly greater adherence to antiviral therapy than patients without positive screens. CONCLUSION: An integrated MH and medical approach was associated with rates of antiviral therapy recommendation and initiation similar to patients without risks for psychiatric or substance use problems. MH care was associated with improved adherence to antiviral therapy. Integrated care offers promise as an approach for addressing psychiatric comorbidity in this traditionally difficult to treat population.