Background: Risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) complications are well-studied. However, risk factors for complications and success after endoscopic sphincterotomy (EST) for duct stones are poorly determined. This study aimed to verify risk factors for mortality, complications, and success after EST. Methods: A multivariate analysis was carried out in a dataset of ERCPs performed during 17 years. Results: A total of5,226 ERCPs were performed, of which 2,137 were in patients with bile duct stones (1,458 women and 679 men; mean age = 57 years) who underwent EST with attempted stone removal. There were 171 (8%) complications, with pancreatitis in 87 (4.1%), bleeding in 48 (2.2%), other complications in 36 (1.8%), and mortality of 0.6%. Successful stone(s) removal was obtained in 2,028 cases (94.9%). On multivariate analysis, mortality was associated with age >60 years (1 vs. 0.2%), cholangitis (4.3 vs. 0.3%), and EST-related complications (5.8 vs. 0.2%). Complications were associated with unsuccessful stone removal (13.4 vs. 7.5%) and difficult cannulation (13.9 vs. 5.4%). An unsuccessful EST was independently related to difficult cannulation (86.2 vs. 98.7%), precutting (79.4 vs. 96.4%), and complications (86.5 vs. 95.6%). Conclusions: Risk factors for complications after EST for stones are delayed bile duct cannulation and failed stone retrieval. Mortality is higher in older patients, those who presented with an EST-related complication, or those who presented initially with cholangitis. Difficult cannulation, EST-related complications, and precutting were associated with an unsuccessful procedure. In this series, outpatient EST with attempted stone retrieval was found to be as safe as performing the procedure in hospitalized patients.