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Background While transpancreatic precut sphincterotomy (TPS) and needle knife precut sphincterotomy (NKS) are advanced ERCP cannulation techniques for difficult biliary access, comparative studies on their efficacies in benign and malignant pathologies remain limited.Methods We performed a retrospective study comparing outcomes of TPS and NKS in patients with difficult biliary access in ERCP. Consecutive patients ≥18 years old who underwent TPS and NKS for difficult biliary access in ERCP for benign and malignant conditions at the Prince of Wales Hospital in Hong Kong between January 2017 and December 2024 were included. Patients with non-native or inaccessible papilla and patients who directly underwent percutaneous biliary drainage or EUS-guided biliary drainage after failed ERCP were excluded. Technical success for precut was defined as successful deep bile duct cannulation confirmed by cholangiogram after precut. Outcome measures include overall first session technical success for biliary cannulation, first session technical success based on benign/malignant pathologies and endoscopist’s ERCP experience, and overall adverse event rate.Results 399 patients (4.4%) of the 9014 ERCP performed between 2017 and 2024 underwent precut (TPS 88, NKS 311) for difficult biliary cannulation. The mean Charlson comorbidity index was comparable between the 2 groups (5.4 vs 5.9, p=0.162). The proportion of patients with benign pathologies was higher in the TPS group but without reaching statistical significance (67.0% vs 59.2%, p=0.181) ( IDDF2026-ABS-0243 Table 1). TPS group had a significantly higher first session biliary cannulation success rate overall (89.8% vs 75.6%, p=0.004), in malignant pathologies (93.1% vs 73.2%, p=0.022), in endoscopists with ERCP experience <1000 and ≥1000 (86.4% vs 70.0%, p<0.001 and 93.2% vs 75.7%, p<0.001, respectively) (IDDF2026-ABS-0243 Table 2). A non-statistically significant trend towards a higher first session biliary cannulation success by TPS was observed in benign pathologies (88.1% vs 77.2%, p=0.068). The overall adverse event rates were comparable between the 2 techniques (12.5% vs 18.0%, p=0.260).Conclusions In this study, TPS achieved a significantly higher overall first session biliary cannulation success for difficult biliary access in ERCP when compared with NKS. The positive impact of TPS was observed in endoscopists with ERCP experience <1000 and ≥1000.Abstract IDDF2026-ABS-0243 Table 1Baseline characteristics of patients who underwent transpancreatic precut sphincterotomy or needle knife precut sphincterotomy for difficult biliary access in ERCPTranspancreatic precut sphincterotomy N = 88Needle knife precut sphincterotomy N = 311p-valueAge (years), mean+/- SD68.9+/-13.871.1+/-13.90.180Gender, male, n (%)51 (58.0)182 (58.5)0.924Charlson Comorbidity Index, mean+/-SD5.4+/-3.25.9+/-3.20.162Indications for ERCP, n (%)Benign etiology59 (67.0)184 (59.2)0.181 CBD stone50 (56.8)170 (54.7)0.720 Benign biliary stricture9 (10.2)9 (2.9)0.007 Bile leak0 (0)4 (1.3)0.580Malignant etiology29 (33.0)127 (40.8)0.181 Pancreatic cancer10 (11.4)50 (16.1)0.314 Cholangiocarcinoma5 (5.7)28 (9.0)0.386 Ampullary cancer0 (0)8 (2.6)0.209 Gallbladder cancer0 (0)6 (1.9)0.346 Malignant biliary obstruction due to lymph node metastasis from other cancers14 (15.9)36 (11.6)0.278Antithrombotic use Anticoagulant*9 (10.2)12 (3.9)0.028 Clopidogrel1 (1.1)3 (1.0)1.000 Aspirin12 (13.6)54 (17.4)0.516SD = standard deviation, CBD = common bile duct*Anticoagulant: warfarin, non-vitamin K antagonist oral anticoagulantsAbstract IDDF2026-ABS-0243 Table 2Outcomes of patients who underwent transpancreatic precut sphincterotomy or needle knife precut sphincterotomy for difficult biliary access in ERCPTranspancreatic precut sphincterotomy N = 88Needle knife precut sphincterotomy N = 311p-valueFirst session technical success, n (%) Overall79 (89.8)235 (75.6)0.004 Benign pathologies52/59 (88.1)142/184 (77.2)0.068 Malignant pathologies27/29 (93.1)93/127 (73.2)0.022 Endoscopist’s ERCP experience < 100038/44 (86.4)7/10 (70.0)< 0.001 Endoscopist’s ERCP experience ≥ 100041/44 (93.2)228/301 (75.7)< 0.001Overall adverse event rate, n (%)11 (12.5)56 (18.0)0.260 Perforation1 (1.1)3 (1.0)1.000 Delayed bleeding1 (1.1)8 (2.6)0.690 Pancreatitis9 (10.2)33 (10.6)1.000 Biliary sepsis2 (2.3)12 (3.9)0.744 Bile leak0 (0)0 (0)- Cardiopulmonary adverse events0 (0)1 (0.3)1.000