Biliary cannulation is an important step in the management of biliary disorders. Despite being a widely performed procedure, cannulation failure remains a significant clinical challenge. Identifying predictive risk factors for failed biliary cannulation is therefore crucial for optimizing endoscopic strategies, improving success rates, and minimizing procedure-related complications.

   This study aims to evaluate the clinical, biological, anatomical, and technical determinants associated with biliary cannulation failure.

   This retrospective, descriptive, single-center study was conducted in our department between November 2020 and November 2025. A total of 74 patients were included, divided into two groups: 37 patients with failed biliary cannulation and 37 patients with successful cannulation.

   Statistical analysis was performed using Jamovi. Univariate analysis was based on the χ² test, and multivariate analysis was conducted using a logistic regression model.

    A total of 74 patients were included. The mean age was 65.5 ± 12.7 years (range: 27–85), with a slight female predominance (female-to-male ratio: 1.3). The leading indication for ERCP was acute cholangitis (36 patients, 48.6%), followed by cholestatic jaundice (23 patients, 31.1%).

   Univariate analysis identified several predictors of biliary cannulation failure, including: cholestatic jaundice as the primary indication for ERCP (p = 0.007); history of hepatobiliary surgery (p = 0.012); bilirubin ≥ 250 mg/L (p = 0.009); leukocytosis ≥ 15,000/mm³ (p = 0.006); moderate-to-severe cholangitis (p < 0.001); presence of a main bile duct stricture (p = 0.004); malignant etiology of the stricture (p = 0.010); tumor type—particularly cholangiocarcinoma and pancreatic malignancies (p = 0.028); and papillary abnormalities, especially peri-diverticular papillae (p = 0.038).

   In multivariate analysis, two factors remained independently associated with cannulation failure: history of hepatobiliary surgery (OR = 8.97; p = 0.033) and papillary abnormalities (OR = 31.68; p = 0.009).

   Among the 37 patients with failed biliary cannulation, 28 (75.7%) underwent second-line intraprocedural salvage techniques, primarily infundibulotomy (25 patients, 67.6%) and, less frequently, precut sphincterotomy (3 patients, 8.1%). These rescue techniques were successful in 75% of cases (21 patients).

   Biliary cannulation failure is influenced by a combination of anatomical, biological, and disease-related factors. Early identification of these risk factors may help tailor endoscopic strategies, improve cannulation success rates, and reduce procedure-related complications.