Background: Post Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis (PEP) can be a significant cause of morbidity, with an incidence of approximately 3.5-9.7% (1). The “Ice water challenge study” conducted in Japan by Azuma et al is the first study to investigate the efficacy of ice water irrigation of the ampulla during ERCP to reduce incidence of PEP (1). This pilot study did not reach statistical significance, however the rate of PEP was reduced from 10% to 4% with the intervention (1). Aim: The aim of this study is to replicate the Japanese trial in an Australian setting with adequate sample size. Methods: A single-blinded cluster randomized controlled trial will be conducted in a tertiary hospital (ethics approval number E22-010-91479). Eligible participants with native ampullas undergoing ERCP will be randomized to 250mls of ice water irrigation through the duodenoscope at the end of the procedure, or control (standard treatment). Demographic and procedural data will be collected. Post-ERCP pancreatitis will be diagnosed clinically according to standard criteria. A lipase level will be taken 2-4 hours post procedure. Results: The primary outcome measure is rate of post-ERCP pancreatitis. A sample size of 779 patients will be required to detect a 50% reduction on PEP (from 10.9% to 5.4%), using a two-sided alpha test with significance level of 0.05. Conclusion: Results of this trial will help to clarify effectiveness of ice water irrigation to reduce rates of this significant post procedural complication in an Australian setting. Azuma S et al. Cooling the papilla with ice water in preventing post-ERCP pancreatitis (ice water challenge study). Surg Endosc. 2022 Aug;36(8)