Objective To explore the efficacy and safety of pancreatic necrosectomy through retroperitoneal approach and omental bursa approach in the treatment of peritoneal infection after severe acute pancreatitis(SAP). Methods The clinical data of 115 patients with peritoneal infection after SAP who underwent pancreatic necrosectomy in the hospital between January 2018 and January 2021 were retrospectively analyzed. According to the surgical approach, the patients were divided into retroperitoneal group(n=55) and omental bursa group(n=60). Clinical treatments of the two groups were compared. Results All patients enrolled successfully underwent the operation. Compared with the omental bursa group, the retroperitoneal group had shorter operation time, less intraoperative blood loss, and shorter first time to eat and hospital stay after operation(P＜0.05). At 3 days after the operation, the levels of white blood cells(WBC), tumor necrosis factor-α(TNF-α), interleukin-8(IL-8), amylase(AMY), and lipase(LPS) were significantly reduced, and these indicators in the retroperitoneal group were significantly lower than those in the omental bursa group(P＜0.05). The total incidence of postoperative complications in the retroperitoneal group was 10.91%, significantly lower than 26.61% in the omental bursa group(P＜0.05). Conclusion Pancreatic necrosectomy through retroperitoneal approach is safe and effective in the treatment of peritoneal infection after SAP. Compared with the omental bursa approach, it has the advantages of shorter operation time, less trauma, milder inflammation and fewer complications.