Background and aims Given the limited data on the safety of endoscopic retrograde cholangiopancreatography (ERCP) in patients with liver cirrhosis, we attempted to evaluate this question using a large national database. Methods We conducted a matched case - control study using the 2010 National Inpatient Sample database in which four non-cirrhotic controls were matched randomly for every cirrhotic patient from the same 10-year age group. We compared adverse events and safety of inpatient ERCP between patients with (n = 3228) and without liver cirrhosis (controls, n = 12 912). Results Of the 3228 cirrhotic patients, 2603 (80.6 %) had decompensated and 625 (19.4 %) had compensated disease. Post-procedure bleeding (2.1 % vs. 1.2 %, P < 0.01) was higher in patients compared to controls. On multivariable analysis, decompensated cirrhosis (adjusted odds ratio [aOR], 2.7; 95 % confidence interval [CI], 2.2 - 3.2), compensated cirrhosis (aOR 2.2; 95 %CI 1.2 - 3.9), therapeutic ERCPs (aOR 1.4; 95 % CI 1.2 - 2.1), and biliary sphincterotomy (aOR 1.6; 95 %CI 1.1 - 2.1) were independently associated with increased risk of post-procedure bleeding. Performing ERCPs in large (aOR 0.5; 95 %CI 0.4 - 0.6) and medium (aOR 0.7; 95 %CI 0.6 - 0.9) sized hospitals was associated with a decreased risk of post-procedure bleeding. Biliary sphincterotomy (aOR 1.7; 95 %CI 1.2 - 2.3) and therapeutic ERCPs (aOR 1.1; 95 %CI 1.1 - 1.3) increased the risk of post-ERCP pancreatitis, and pancreatic stent placement was associated with a decreased risk of post-ERCP pancreatitis (aOR 0.8; 95 %CI 0.7 - 0.9). Conclusions Cirrhosis (both compensated and decompensated), performing therapeutic ERCPs and biliary sphincterotomy increase the risk of post-procedure bleeding. Performing ERCPs in large and medium sized hospitals may improve outcomes.