Many patients are excluded from HCV treatment due to psychiatric issues (PI) and substance abuse (SA). We sought to determine deferral rates and reasons for nontreatment, determine whether patients initially deferred for PI or SA subsequently received antiviral therapy, and compare treatment outcomes of these patients with patients who were not deferred. A retrospective analysis of 433 patients with HCV was conducted. Seventy-five percent of patients were deferred from treatment. Primary deferral reasons were PI (34.3%) and SA (33.6%). Characteristics were similar between eligible and ineligible treatment candidates. Of those initially deferred from therapy, over half returned for follow-up; however, only 13% eventually received treatment. Patients initially deferred for PI/SA but subsequently treated were less likely to complete treatment than patients without these comorbidities (48% vs. 13%). SVR was lower in patients with PI/SA compared to those without (26% vs. 47%). Deferral rates for PI/SA remain high, and these patients are rarely treated at subsequent clinic visits. When patients are deferred for PI/SA but later treated, they have significantly higher rates of not completing treatment and a trend toward lower SVR rates.