Papilla morphology has been proposed as an anatomical determinant of difficulty in ERCP cannulation and in post-ERCP pancreatitis (PEP) risk, but evidence regarding its predictive value remains inconsistent. We examined whether papilla type and the presence of periampullary diverticulum are associated with PEP in a large cohort of ERCP-naïve patients.

A retrospective analysis was conducted on 891 ERCPs that were performed on ERCP-naïve patients at General State Hospital of Athens " G. Gennimatas ’’ during a three-year span. We included only ERCP-naïve patients with non-pathologic papillae; papillary adenomas and inflammatory or distorted ones were excluded from the study. Papillae were classified according to the Haraldsson classification as type I (normal), type II (small), type III (protruding) and type IV (creased/ridged).  The diagnosis of PEP was determined according to the ESGE diagnostic criteria. Logistic regression assessed the association between papilla type and PEP while Chi-Square (χ²) tests were used to evaluate differences in PEP incidence across papilla types and the effect of diverticulum presence on PEP risk. Statistical analyses were performed using SPSS v.23.

The papillae type distribution was: Type 1=83.4%, Type 2=8,1%, Type 3=7,4% and Type 4=1,1%. Overall PEP incidence was 6.6%. Chi-square analysis demonstrated a statistically significant overall difference in PEP incidence across the four types (p=0,026). Post-hoc pairwise comparisons showed that Type 3 papillae differed significantly from Type 1 and Type 2 (both p < 0.05). The Type 3 vs Type 4 comparison could not be reliably assessed by χ² due to sparse data (only 1 PEP case in Type 4). After logistic regression it was shown that Haraldsson type 3 papilla independently increased the odds of PEP (p = 0.009; OR 2.83, 95% CI 1.31–6.16). Presence of periampullary diverticulum was recorded in 11.7% of cases, but it was not associated with PEP (p = 0.94).

In this large ERCP-naïve cohort, Haraldsson Type 3 papilla emerged as a significant predictor of PEP, whereas periampullary diverticulum had no impact on risk of PEP. These findings support evidence stating that differences in papilla morphology are linked with alterations in cannulation complexity and PEP. Papilla morphology may represent a simple, visually accessible parameter to enhance pre-procedural risk stratification and guide PEP-prevention strategies.