Background/Objectives: Direct‑acting antivirals (DAAs) cure hepatitis C virus (HCV) infection and may improve health‑related quality of life (HRQoL), but responsiveness differs across instruments. We quantified longitudinal changes using EQ‑5D‑5L, SF‑8 and CLDQ in a multicenter Japanese cohort. Methods: Adults with chronic HCV completed patient‑reported outcomes (PROs) at baseline and 12/24/36 weeks (48 weeks where available). Complete‑case panels were defined per instrument (SF‑8 n=112, CLDQ n=131, EQ‑5D‑5L n=128). Domain trajectories were summarized and compared with baseline. Results: SF‑8 improved by 36 weeks: General Health 50.42→52.47, Vitality 50.73→52.55, Mental Health 51.02→53.05. CLDQ improved in Worry 5.21→5.82 and Total 5.21→5.47. EQ‑5D‑5L utilities remained high and stable (0.913→0.920), consistent with ceiling effects at high baseline health. External real‑world data indicated better on‑treatment HRQoL with ribavirin‑free regimens. Conclusions: Interferon‑free DAAs yield early, clinically meaningful HRQoL gains in symptom‑proximal and mental domains, while generic utilities show minimal short‑term change. Combining disease‑specific PROs with utilities is essential for patient‑centered care and for parameterizing cost‑utility models in Japan.