Background & Aims: Large-scale data regarding the real-world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) for patients with chronic hepatitis C virus (HCV) infection were limited in East Asia. We aimed to evaluate the clinical performance of GLE/PIB in different HCV populations in Taiwan., Methods: A total of 658 chronic HCV patients with compensated liver diseases receiving GLE/PIB for 8 (n = 549), 12 (n = 103) or 16 (n = 6) weeks were retrospectively enrolled. The effectiveness was determined by sustained virologic response at off-therapy 12 weeks (SVR 12 ). Patient characteristics potentially related to SVR 12 and the safety profiles were also assessed., Results: By evaluable population (EP) and per-protocol (PP) analyses, the overall SVR 12 rate was 98.2% (95% confidence interval (CI): 96.8%-99.0%) and 99.4% (95% CI: 98.4%-99.8%). The SVR 12 rates were 98.9% (95% CI: 97.6%-99.5%), 94.2% (95% CI: 87.9%-97.3%) and 100% (95% CI: 60.1%-100%) in patients receiving 8, 12 and 16 weeks of treatment respectively. A total of 656 (99.7%) patients completed the scheduled treatment. The SVR 12 rates were comparable regardless of baseline characteristics or week 4 viral decline. Twenty (3.0%) patients had serious adverse events (AEs), but none were not related to GLE/PIB. The two most common AEs were pruritus (7.8%) and fatigue (5.5%). Two (0.3%) and no patients had ≥3-fold upper limit of normal (ULN) for total bilirubin and alanine aminotransferase (ALT) levels., Conclusions: GLE/PIB for 8-16 weeks is effective and well-tolerated for patients with chronic HCV infection in Taiwan., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)