Background:Evidence shows that rectal indomethacin (RI) reduces the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients. The prophylactic role of RI in low-risk patients has not yet been identified. The objective of our study was to evaluate the impact of RI in preventing PEP in low-risk patients.Methods:A retrospective cohort study was conducted to evaluate the impact of RI in preventing PEP. RI was available starting November 2012. Patient characteristics and procedure details were collected.Results:The study population included 2238 patients who underwent ERCP (1055 in the RI group and 1183 in the control group). PEP was diagnosed in 107 patients (4.8%). In a multivariate model of consecutive patients, RI reduced the incidence of PEP by 55% (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.36-0.94; P=0.03). In a multivariate model that included 1874 (84%) low-risk patients, RI reduced the incidence of PEP by 62% (OR 0.38, 95%CI 0.19-0.74; P=0.004). Propensity-matched group analysis was performed for low-risk native papilla patients. RI reduced the incidence of PEP by 61% (OR 0.39, 95%CI 0.18-0.8; P=0.009).Conclusion:RI reduced PEP in consecutive as well as low-risk patients. RI should be administrated in consecutive patients unless contraindicated. Larger prospective studies are needed to confirm our results.