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Introduction Transpancreatic biliary sphincterotomy (TPBS) may be used to facilitate bile duct cannulation at ERCP when standard cannulation techniques fail. This technique involves performing a sphincterotomy after a guidewire is inserted into the main pancreatic duct (PD) to expose the bile duct orifice. We report a 5-year experience of TPBS from a large UK tertiary referral centre.Methods This was a single centre, retrospective review of all ERCPs requiring TPBS to achieve biliary access over a 5-year period (October 2020 to October 2025). Data was obtained from the local endoscopy database and electronic medical notes. Technical success, defined as successful biliary cannulation after TPBS without the need for additional advanced cannulation techniques, and adverse event rates were recorded and assessed.Results Out of 2412 ERCPs performed in this 5-year period, 88 (3.6%) ERCP cases were identified where TPBS was performed to gain biliary access at ERCP. Mean patient age was 63.7 years old (range: 14 – 93), with a female preponderance (49/88). 54/88 (61.4%) were local referrals and 34/88 (38.6%) tertiary referrals. 66/88 (75%) had ERCP performed due to benign conditions, 22/88 (25%) were due to malignant pathology. 15/88 (17%) of patients had a previous failed ERCP attempt.TPBS was performed by 3 consultants during the study period. 85/88 patients had per rectal diclofenac immediately prior to ERCP. Prophylactic PD stent was placed after TPBS in majority of cases (85/88). Technical success was achieved in 79/88 (89.8%) of cases.In the 9 unsuccessful cases, 6 were associated with malignant pathology and 3 with benign disease. 1 patient died due to cancer progression prior to reattempted ERCP. During the index session, 1 patient underwent successful EUS guided biliary drainage, 1 had a failed EUS rendezvous and was conservatively managed. 6 patients underwent repeat ERCP, with successful biliary cannulation achieved in 3/6 cases. 3 cases were unsuccessful – with 2 managed conservatively (bile leak =1, stone disease =1) and 1 undergoing successful same-session EUS guided choledochoduodenostomy.Overall adverse event rate was 6/88 (6.8%), all due to post-ERCP pancreatitis. 5/6 cases were mild and 1/6 case was moderate based on Cotton Grading. There were no cases of post-ERCP bleeding or perforation. 30-day mortality was 2/88 (2.3%), these were related to progression of malignant disease rather than procedure-related.Conclusions TPBS is an effective technique to achieve biliary cannulation when standard cannulation techniques fail. When combined with prophylactic PD stenting and pre-procedure per rectal NSAIDs, TPBS appears safe, with an acceptable rate of adverse events in a tertiary-centre setting.