Pancreatic necrosectomy remains an important treatment modality for the management of infected pancreatic necrosis but is associated with significant mortality. The aim of this study was to identify factors associated with mortality following pancreatic necrosectomy. Patients who underwent pancreatic necrosectomy from January 1995 to December 2004 were reviewed. The association between admission, preoperative and postoperative variables, and mortality was assessed using logistic regression analysis. A total of 1248 patients presented with acute pancreatitis, of whom 94 (7.5%) underwent pancreatic necrosectomy (51 men, 43 women). The preoperative median Acute Physiology, Age, and Chronic Health Evaluation (APACHE II) score was 9 (range 2-19). The median cumulative organ dysfunction score was 2 (0-9) preoperatively and 4 (1-11) postoperatively. In all, 23 patients (24.5%) died. Those who died were older than the survivors; the ages (median and range) were 69 years (40-80 years) versus 52 years (19-79 years) (p < 0.05). They also had higher admission APACHE II scores (median and range): 14 (12-19) versus 9 (2-22) (p < 0.001). There were significant associations between preoperative (p < 0.01) and postoperative (p < 0.01) Marshall scores and mortality following pancreatic necrosectomy. The presence of the systemic inflammatory response syndrome (SIRS) during the first 48 hours (p < 0.01) and the time between presentation and necrosectomy (p < 0.01) were independent predictors of survival. Pancreatic necrosectomy is associated with higher mortality in patients with increased APACHE II scores, early persistent SIRS, and unresolved multiorgan dysfunction. Necrosectomy is associated with poorer outcome when performed within 2 weeks of presentation.