Background and Aims Patients with cirrhosis may be less than optimal candidates for ERCP because of underlying ascites, coagulopathy, encephalopathy, and other problems. Although the risks of surgery in patients with cirrhosis are well known, few data are available regarding ERCP in patients with cirrhosis. We performed a retrospective, multicenter study of ERCP in patients with cirrhosis to evaluate outcomes, efficacy, and safety. Methods Multicenter retrospective study. Results A total of 538 ERCP procedures were performed on 328 patients with cirrhosis. A total of 229 patients had Child-Pugh (CP) class A, 229 patients had CP class B, and 80 patients had CP class C. Thrombocytopenia and coagulopathy were corrected before ERCP. The 30-day, procedure-related adverse events included post-ERCP pancreatitis (n = 25, 4.6%: 21 mild, 3 moderate, 1 severe), hemorrhage (n = 6, 1.1%), cholangitis (n = 15, 2.8%), perforation (n = 2, 0.4%), aspiration pneumonia (n = 5, 0.9%), bile leakage (n = 1, 0.2%), cholecystitis (n = 1, 0.2%), and death (n = 1, 0.2%). There was a higher incidence of adverse events in patients with CP class B and C disease when compared with those with CP class A disease (11.4%, 11.3%, and 6.1%, respectively; P =.048). There was no correlation between the risk of significant hemorrhage and the presence of coagulopathy or CP class, even in those who underwent a sphincterotomy. The presence of poorly controlled encephalopathy correlated with a higher overall adverse event rate (P =.003). Sub-analysis revealed that patients without primary sclerosing cholangitis had a significantly higher overall rate of adverse events, pancreatitis, bleeding, and cardiopulmonary adverse events after ERCP when compared with those with primary sclerosing cholangitis. Conclusions Our study was performed on a large series of patients with cirrhosis undergoing ERCP. Overall, the adverse events seen in patients with cirrhosis are similar to those seen in the general population of patients undergoing ERCP, although patients with CP classes B and C have higher adverse event rates compared with those with CP class A. Patients with cirrhosis without primary sclerosing cholangitis had significantly greater adverse event rates when compared with patients with primary sclerosing cholangitis.