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Patients with primary sclerosing cholangitis (PSC) have an increased risk for adverse events following endoscopic retrograde cholangiopancreatography (ERCP), mainly caused by bacterial cholangitis. The risk of pancreatitis is less examined. Therefore, our aim was to study adverse events following ERCP and to evaluate if PSC is a risk factor for pancreatitis.Data were collected through a Swedish nationwide quality registry comprising fifty-one Swedish ERCP centres. The final study cohort consisted of 8932 adults who had undergone ERCP from 1 January 2007 to 31 December 2009. A total of 141 patients had PSC. Variables of importance for adverse events were entered into a multivariate logistic regression model for risk factor analysis.The following adverse events were increased in PSC as compared with non-PSC patients: overall (18.4% vs. 7.3%), pancreatitis (7.8% vs. 3.2%, P = 0.002), cholangitis (7.1% vs. 2.1%, P < 0.001) and per-operative extravasation of contrast (5.7% vs. 0.7%, P < 0.001). PSC was shown to be an independent risk factor for all of these adverse events: pancreatitis, OR 2.02 (95% CI, 1.04–3.92), cholangitis, OR 2.88 (95% CI, 1.47–5.65), and extravasation of contrast, OR 5.84 (95% CI, 2.24–15.23).The rate of adverse events overall following ERCP in PSC is 18% and PEP occurs in 8%. PSC is an independent risk factor for PEP and the risk is doubled. These findings underline the importance of a careful selection of PSC patients eligible for ERCP as well as a need for high competence of the treating team.