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Background and Study Aim: The commonly used minimally invasive methods for patients with infected pancreatic necrosis (IPN) are initial endoscopic transluminal drainage (ETD) and percutaneous catheter drainage (PCD), which are followed, if necessary, by endoscopic or surgical necrosectomy. This study intends to explore which of the two minimally invasive treatments leads to a better prognosis.Patients and Methods: Patients with IPN and an indication for intervention were prospectively enrolled and underwent either initial ETD or PCD followed, if necessary, by endoscopic or surgical necrosectomy.Results: Initial treatment success occurred in 8 of 11 patients after ETD (72.7%) and in 3 of 13 patients after PCD (30.8%) (risk ratio [RR] with ETD, 2.36; 95% CI 0.97-5.77; P = 0.04). After 1 year of follow-up, 72.7% of patients survived with ETD, and 69.2% survived with PCD (RR 1.05; 95% CI 0.63-1.75; P = 0.85). Intestinal fistula seems to have occurred less in the patients who received initial ETD rather than PCD therapy (9.1 vs. 38.5%; RR 0.24; 95% CI 0.03-1.73; P = 0.098). Fewer patients who underwent an initial ETD were transferred to surgery (9.1 vs. 46.2%; RR 0.20; 95% CI 0.03-1.40; P = 0.047). A higher rate of new-onset diabetes (3 cases) or impaired glucose tolerance (1 case) occurred in initial PCD compared to ETD (40 vs. 0%, P = 0.042).Conclusion: The outcomes of initial endoscopic transluminal drainage are superior to percutaneous drainage for patients with infected pancreatic necrosis (ChiCTR-ONRC-13003653). [ABSTRACT FROM AUTHOR]