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Objectives: ERCP is essential in managing pancreaticobiliary disease, with well-documented complications. Rates of clinically significant complications are about 10%, approximately half of which is related to post-ERCP pancreatitis (PEP). We aimed to quantify the effect of previous sphincterotomy on post-endoiscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP)., Materials and Methods: Data were collated from a contemporaneously collected database of 2876 consecutive ERCP procedures of a single operator in a tertiary referral centre. Analysis was conducted using R software, and logistic regression models., Results: Of 2876 procedures (mean age 63 years, 56% female), 120 (4.2%) developed PEP and 268 (9.3%) had prolonged/unplanned hospital admission. Univariate analysis showed patients with previous sphincterotomy 28/1054 (2.7%) had decreased risk of PEP compared with those without sphincterotomy 92/1822 (5.0%) (OR 0.52, p  = .0021). This difference was not evident when multivariate analysis for age, sex and indication was undertaken due to a particularly low risk of PEP in stent change patients (1.4%), which were disproportionately represented in the previous sphincterotomy group. The rate of prolonged/unplanned hospital admission was recorded for a total of 2876 patients, occurring in 184/1802 (10.1%) in the native ampulla group, versus 84/1045 (8.0%) in the previous sphincterotomy group., Conclusions: The risk of PEP is halved by prior sphincterotomy. The presence of a biliary stent conferred an even lower risk of PEP (1.4%), but those without an in situ stent at the time of ERCP had a similar risk of PEP (4.6%) of prolonged/unplanned hospitalisation to those with a native ampulla.