Objective To observe the clinical outcomes and safety of continuous negative pressure irrigation (NPI) and endoscopic necrosectomy(ED) for treating infected pancreatic necrosis(IPN). Methods A retrospective review of the data of 163 severe acute pancreatitis(SAP) patients with IPN who were treated by four-step drainage from January 2012 to December 2013 at the SAP therapy center of Nanjing General Hospital was performed. All patients were divided into 7 groups including PCD alone, PCD+NPI, PCD+NPI+ED, PCD+ON, PCD +NPI +ON, PCD +ED +ON and PCD +NPI +ED +ON group based on the drainage strategy of percutaneous catheterdrainage(PCD),NPI, ED and open necrosectomy(ON), and the feasibility and safety were analyzed. Results All the patients underwent PCD therapy. Each patient underwent a median of 3 drainageprocedures and the median total drainage duration was 11 days. No significant procedure-related complication was observed. Around 40% of the patients recovered after receiving PCD alone. Thirty-four patients(20.9%) underwent ON. The mean hospitalization duration was 38 days and the mean ICU stay was 19 days. There were 25 cases with new-onset organ functional failure,26 patients with sepsis,32 patients with gastric and intestinal fistula,34 patients with intra-abdominal bleeding,8 patients with portal veinthrombosis and 3 patients with gastric outlet obstruction. 28 patients(17.2%) died. Conclusions This four-step approach is effective in treating IPN when compared with other step-up strategies. NPI and ED could offer distinct clinical efficacy without adding no extra risk to patients.