In an urban referral clinic, 182 hepatitis C-infected adults including 110 (60%) with HIV coinfection were evaluated for pegylated interferon and ribavirin therapy. Overall, only 33% were eligible for treatment. Considering all patients together, the major barriers to treatment were nonadherence with the evaluation process (23%), refusal of treatment (10%), active substance abuse (9%), and medical contraindication (8%). There was a trend toward a higher rate of treatment eligibility in HIV coinfected patients (39% vs. 25%; p = 0.07), who were significantly more likely to be adherent with the evaluation process compared to those with hepatitis C alone (86% vs. 63%; p = <0.001). Acceptance of antiviral therapy for hepatitis C was similar between eligible persons with and without HIV. These findings highlight the need to develop interventions to improve adherence and to manage substance abuse and other comorbidities in order to maximize the impact of interferon and ribavirin therapy on urban patients with hepatitis C.