Background: One of the most feared complications of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of 3.5 to 15%, is post ERCP pancreatitis (PEP). Given the role of statins in the reduction of systemic and pancreatic intraluminal inflammation, we hypothesized that the use of statins may lower the risk of PEP. Methods: A retrospective cohort study of all patients undergoing ERCP at West Virginia University during the years 2016 and 2017 was performed. Possible association of collected variables with PEP was assessed with Univariate tests and multivariable logistic regression analyses. Results: A total of 1162 ERCPs were included. Mean age was 60.12 years (SD: 17.5). 51.3% of the participants were female. Two hundred and sixty-three participants underwent more than one ERCP during the study period. Seven hundred and ninety-nine ERCPs (78.8%) were conducted in participants who were not taking a statin medication at the time of ERCP, while 363 participants were on statin medications at the time of ERCP; 118 and 245 participants were taking high dose statins (atorvastatin 40-80 mg or rosuvastatin 20 mg), and low/medium dose statins (all other statin regimens) at the time of the procedure, respectively. The overall incidence of PEP in the cohort was 7.3%. In the non-statin and statin groups, 9.5 and 3.4% of participants developed PEP, respectively. On univariate analysis, young age, no statin use, history of PEP, and endoscopic sphincterotomy were found to be significantly associated with the development of PEP. In a binary logistic regression model, young age (P = 0.033), history of PEP (P = 0.0001, OR 2.41, 95% CI: 1.05-5.51) and endoscopic sphincterotomy (P = 0.038, OR 2.85, 95% CI: 1.7-4.78) were found to be associated with increased risk of PEP. Statin usage was found to be protective against PEP, (OR 0.35, 95% CI: 0.18-0.69). Conclusion: Chronic statin usage is protective against post ERCP pancreatitis, and our findings suggest a potential role of these drugs as prophylactic agents. Randomized controlled trials are needed to establish any potential clinical application.