OBJECTIVE: To examine the surgical indications and clinical outcomes of a large cohort of patients with necrotizing pancreatitis. SUMMARY BACKGROUND DATA: Mortality after debridement for necrotizing pancreatitis continues to be inordinately high. The clinical experience with patients who underwent uniform surgical treatment for necrotizing pancreatitis at the Massachusetts General Hospital over a 15-year period is described. METHODS: Retrospective review of 167 patients with necrotizing pancreatitis who required intervention and were treated with single stage debridement and a closed packing technique. Particular emphasis was placed on the indication for surgery and the presence of infected necrosis. Multiple logistic regression models were used to identify predictors of mortality. RESULTS: The primary preoperative indication for operation was infected necrosis (51%), but intraoperative cultures proved that 72% of the entire cohort was infected. The rate of reoperation was 12.6%, and 29.9% of patients required percutaneous interventional radiology drainage after initial debridement. Overall operative mortality was 11.4% (19/167), but higher in patients who were operated upon before 28 days (20.3% vs. 5.1%, P = 0.002). Other important predictors of mortality included organ failure ≥3 (OR = 2.4, P = 0.001), postoperative intensive care unit stay ≥6 days (OR = 15.9, P = 0.001), and female gender (OR = 5.41, P = 0.02). CONCLUSIONS: Open, transperitoneal debridement followed by closed packing and drainage results in the lowest reported mortality and reoperation rates, and provides a standard for comparing other methods of treatment. A negative FNA does not reliably rule out infection. The clinical status of the patients and not proof of infection should determine the need for debridement. © 2008 Lippincott Williams & Wilkins, Inc.