Objective: To investigate the clinical efficacy of endoscopic plus laparoscopic treatment for severe acute pancreatitis (SAP) complicated by pancreatic pseudocyst (PPC). Methods: The clinical data of 52 patients with SAP and PPC undergoing surgical treatment from June 2012 to March 2014 were collected. Of the patients, 31 cases underwent endoscopic plus laparoscopic treatment (endoscopic-laparoscopic group), and 21 cases were subjected to open surgery (open surgery group). The intraoperative conditions, postoperative outcome and recovery as well as incidence of complications were compared between the two groups. Results: In endoscopic-laparoscopic group, the operative time, intraoperative blood loss, time to first flatus and length of postoperative hospital stay were significantly decreased compared with open surgery group (all P<0.05). There was on statistical difference in treatment efficacy rate and incidence of postoperative complications between the two groups (both P>0.05). The incidences of postoperative pain, nausea and vomiting in endoscopic-laparoscopic group were significantly lower than those in open surgery group (all P<0.05). Postoperative follow-up was conducted for 6 months, and no PPC recurrence was noted in any of the two groups. Conclusion: Endoscopic plus laparoscopic procedure has remarkable efficacy and better safety in treatment of SAP with PPC, and individualized treatment strategies can be formulated according to the specific condition of patients. So it is recommended to be used in clinical practice.