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Background: Direct‐acting antiviral agents (DAAs) have transformed chronic hepatitis C (CHC) treatment. Continued affordable access to DAAs requires updated cost‐effectiveness analyses (CEA). Utility is a preference‐based measure of health‐related quality of life (HRQoL) used in CEA. This study evaluated the impact of DAAs on utilities for patients with CHC in two clinical settings. Methods: This prospective longitudinal study included patients aged ≥18 years, diagnosed with CHC and scheduled to begin DAA treatment, from two tertiary care hospital clinics and four community clinics in Toronto, Calgary, and Montreal. Patients completed two utility instruments (EQ‐5D‐5L and Health Utilities Index 2/3 (HUI2/3)) before treatment, 6 weeks after treatment initiation, and 12 weeks and 1 year after treatment completion. We measured utilities for all patients, and for hospital‐based and community‐based groups. Results: Between 2017 and 2020, 209 patients (126 hospital‐based, 83 community‐based; average age 53 years; 65% male) were recruited, and 143 completed the 1‐year post‐treatment assessment. Pre‐treatment, utilities were (mean ± standard deviation) 0.77 ± 0.21 (EQ‐5D‐5L), 0.69 ± 0.24 (HUI2) and 0.58 ± 0.34 (HUI3). The mean changes at 1‐year post‐treatment were 0.035, 0.038 and 0.071, respectively. While utilities for hospital‐based patients steadily improved, utilities for the community‐based cohort improved between baseline and 12‐weeks post‐treatment, but decreased thereafter. Discussion: This study suggests that utilities improve after DAA treatment in patients with CHC in a variety of settings. However, community‐based patients may face challenges related to comorbid health and social conditions that are not meaningfully addressed by treatment. Our study is essential for valuing health outcomes in CHC‐related CEA. [ABSTRACT FROM AUTHOR]