Objective: To investigate the clinical efficacy and safety of debridement of necrotic pancreatic tissue and drainage via retroperitoneal approach in management of infected pancreatic necrosis. Methods: Forty-four patients with infected pancreatic necrosis undergoing necrosectomy and drainage via retroperitoneal approach during 2013 to 2015 were enrolled as observational group, and previous 56 patients with the same condition undergoing necrosectomy via abdominal incision and then closed continuous irrigation served as control group. The treatment results between the two groups of patients were compared. Results: The general data and all laboratory indexes before operation between the two groups had no statistical difference (all P>0.05). The levels of serum amylase, urine amylase, blood sugar, procalcitonin, TNF-α and IL-8 in observational group were all significantly lower than those in control group after operation (all P<0.05). The operative time and length of hospital stay in observational group were significantly reduced compared with control group (both P<0.05). The rate of reoperation and death or treatment abandonment had no statistical difference between the two groups (both P>0.05). In observational group compared with control group, the effective rate was increased (75.0% vs. 58.9%) and incidence of surgical complications was decreased (15.9% vs. 33.9%), but both differences did not reach statistical significance (both P>0.05). Conclusion: Necrosectomy and drainage via retroperitoneal approach for infected pancreatic necrosis has reliable efficacy, and with faster recovery and less invasiveness than open surgery.