The real-world cure rates for hepatitis C (HCV) with direct-acting antivirals (DAAs) based on intention-to-treat (ITT) analysis may be lower than reported in the literature because of non-compliance.To determine whether patients treated in a structured outpatient HCV clinic (SHC) had higher compliance and treatment success rates compared to those treated in general hepatology clinics (GHC).In this study, we compared the treatment and compliance success rates of 488 and 840 patients treated in the SHC and GHC, respectively. The SHC required a pre-treatment clinic visit when patients picked up their initial medication, and received detailed education of the treatment plan and follow-up. In the GHC, the medications were delivered to patients' homes, and there was less formal education. Compliance success was defined as a combination of treatment completion and obtaining at least 1 post-treatment viral load at week 4 or 12. Treatment success was defined as either SVR4 or SVR12.Fifty of 488 (10.3%) patients from the SHC and 163 of 840 (19.4%) patients from the GHC were lost to follow-up (P < .0001). sustained virological response (SVR) rates were similar in compliant patients in both the SHC (419/438, 95.6%) and GHC (642/677, 94.8%), but treatment success rates by intention to treat (ITT) (overall 79.9%) were higher in SHC compared to GHC (85.9% vs 76.4%, P < .0001). Multivariate analysis showed that female patients (P = .01), older age (P = .0005), treatment in SHC (OR 1.7, 95% CI 1.2, 2.3, P = .0008), and sofosbuvir/simeprevir compared to sofosbuvir/ledipasvir had higher odds of compliance success; elbasvir/grazoprevir or dasabuvir/ombitasvir/paritaprevir/ritonavir had lower odds of compliance success compared to sofosbuvir/ledipasvir. Female patients (P = .02), older age (P < .0001), previous treatment (P = .03), treatment in SHC (OR 1.7, 95% CI 1.2, 2.3, P = .0008), and sofosbuvir/ledipasvir compared to sofosbuvir/velpatasvir, sofosbuvir, or elbasvir/grazoprevir had higher odds of treatment success. With 1:1 matching, the SHC group still had significantly higher odds than the GHC group of achieving treatment and compliance success.Our study shows that the effectiveness of HCV treatment could be improved by coordinating treatment in a structured HCV clinic.