Glecaprevir/pibrentasvir is a pangenotypic direct-acting antiviral regimen approved for treating chronic hepatitis C virus. Real-world use of protease-inhibitor-containing regimens requires further evaluation in patients with cirrhosis. We evaluated the real-world safety and effectiveness of glecaprevir/pibrentasvir in patients with cirrhosis from the German Hepatitis C-Registry who initiated treatment between 2 August 2017-30 June 2019. Overall, 131 patients received 12-week (on-label) treatment and 51 received 8-week (off-label) treatment. No patient discontinued treatment due to adverse events. Four patients had serious adverse events; none were considered related to glecaprevir/pibrentasvir. Two patients had total bilirubin >5 x upper limit of normal (ULN) during treatment. Three patients had alanine aminotransferase and 3 patients had aspartate aminotransferase >3 x ULN. Rates of sustained virologic response were 100% (86/86) for 86 patients with available data. Glecaprevir/pibrentasvir treatment was well-tolerated and highly effective in patients with chronic hepatitis C and cirrhosis in real-world practice.