Current guidelines recommend delaying endoscopic drainage until at least 4 weeks after the onset of acute necrotizing pancreatitis. However, in clinical practice, "early" drainage is sometimes considered for acute infected collections, despite a lack of strong supporting evidence. The primary objective of this study was to compare the clinical efficacy and safety of “early” versus “delayed” endoscopic drainage of necrotic pancreatic collections.

Patients with necrotizing pancreatitis and pancreatic collections treated with "early" endoscopic drainage (<4 weeks) in a multicentre retrospective cohort (2010–2025) were compared with patients undergoing "late" drainage (≥4 weeks) from a recent multicentre randomized controlled trial (PROMETHEUS, NCT03100578). A propensity score analysis using Inverse Probability of Treatment Weighting (IPTW) was performed to minimize confounding (age, sex, infection status, ASA score). The primary outcome was the need for surgical rescue. Secondary outcomes included clinical success, number of endoscopic sessions, procedure-related adverse events, and mortality.

From a total of 648 patients screened who underwent endoscopic drainage, 107 were included in the analysis: 43 in the "early" group and 64 in the "late" group. Median age was 60–65 years in both groups. The predominant aetiology was biliary pancreatitis. Confounding factors were adequately balanced after IPTW adjustment. In descriptive analysis, the need for surgical rescue was numerically higher in the "early" group, but this difference was not significant after propensity score adjustment. Early and overall adverse events were higher in the "late" group, reaching statistical significance in the propensity analysis but not in the descriptive analysis. No significant differences in mortality or clinical success were observed in either analysis. The necrosectomy rate was significantly higher in the "early" drainage group in both descriptive and propensity-adjusted analyses.

Clinical outcomes were comparable between early and late endoscopic drainage in terms of surgical rescue, clinical success, and mortality. The "early" group required a greater number of endoscopic sessions and more frequent necrosectomy. Major adverse events were more frequent in the "late" group on propensity analysis. These findings suggest that early drainage may be a reasonable option in selected patients, although the comparison of retrospective data with RCT data represents an inherent limitation that warrants cautious interpretation.