The optimal timing of endoscopic retrograde cholangiopancreatography (ERCP) in pancreatitis remains debated, especially in patients without cholangitis or persistent biliary obstruction. This study evaluated technical outcomes, procedural complexity, and adverse events of ERCP performed during the acute phase of pancreatitis compared with ERCP undertaken after clinical and biochemical resolution.

In this retrospective real-world study, consecutive ERCPs performed for pancreatitis at two high-volume hepatopancreatobiliary centers (January 2001–July 2025) were reviewed. Among 5,983 ERCPs, 344 met inclusion criteria. Patients were categorized into: Group A (acute pancreatitis with cholangitis and/or elevated bilirubin; n=114) and Group B (post-acute ERCP performed after resolution of abdominal pain and normalization of amylase <3× normal; n=230). Demographic, imaging, procedural, and outcome variables were analyzed. Primary endpoints were biliary cannulation success, duct clearance, and ERCP-related adverse events.

Overall, successful biliary cannulation was achieved in 309/344 patients (89.8%), increasing to 93.9% when excluding the 15 patients in whom the papilla could not be reached. Cannulation success did not significantly differ between acute and post-acute ERCP (93.0% vs 88.3%; p=0.114). However, procedures in the post-acute group were technically more demanding, with higher rates of precut fistulotomy (33.8% vs 25.2%; p=0.040) and >5 cannulation attempts (54.1% vs 41.4%; p=0.017). Choledocholithiasis was present in 46.8% of patients and the majority of stones were <1.5 cm. Complete bile duct clearance was achieved in 140/154 (90.9%) patients, with no significant difference between groups (92.7% vs 89.9%; p=0.468). Periampullary diverticula were significantly more common in the post-acute group, whereas an inflamed papilla was more frequent during the acute phase. ERCP-related adverse events were uncommon overall (17/344; 4.9%) and tended to be more frequent in the post-acute group (6.1% vs 2.6%; p=0.128). Intraprocedural bleeding occurred significantly more often post-acutely (37.8% vs 28.1%; p=0.047), paralleling the increased procedural complexity. Post-ERCP pancreatitis was observed only in Group B (6/230; 2.6%), while other specific events, including perforation (0.3%), clinically significant bleeding (0.9%), cholecystitis (0.6%) and sedation-related serious adverse events (0.3%) were rare. Mortality occurred exclusively in the acute group (4/114; 3.5%; p=0.012) and was largely attributed to severe underlying pancreatitis rather than the procedure itself.

In this large, long-term real-world cohort, ERCP performed during either the acute or post-acute phase of pancreatitis achieved high biliary cannulation and duct clearance rates with low overall complication rates when undertaken by experienced endoscopists. These findings suggest that procedural complexity and baseline disease severity, rather than timing alone, are the principal determinants of ERCP risk in pancreatitis-associated indications.