Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)–infected patients who are direct‐acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real‐world experience with 8‐week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8‐week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention‐to‐treat population and 99.3% (526/530) in the per‐protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8‐week treatment with G/P, none had baseline polymorphisms or treatment‐emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment‐emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug‐related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA‐naïve noncirrhotic genotype 1 or 2 patients in a real‐world clinical setting in Japan.