Percutaneous or endoscopic drainage was usually performed as the first step in step-up approach for infected pancreatic necrosis (IPN). However, drainage was unnecessary or unavailable in some patients. To estimate the safety and effect of one-step laparoscopic-assisted necrosectomy in IPN patients. A retrospective analysis of IPN patients received surgical therapy in our center between January 2015 and December 2017 was performed. Patients were assigned to either one-step or step-up groups according to the received therapeutic approach. Incidence of complications, death, total number of interventions, and total hospital stay were compared. Logistic regression and nomogram were used to explore the risk factors and probability for patients undergoing interventions ≥3 times. There were 45 and 49 patients included in one-step and step-up groups, respectively. No significant difference between groups in terms of new organ failure (14.29 vs. 14.33%, p = 0.832), death (8.89 vs.8.17%, p = 0.949), and long-term complications (18.37 vs. 15.56%, p = 0.717). However, the number of interventions in one-step group was significantly less than in step-up group with shorter hospital stay. After multivariate analysis, C-reactive protein, interleukin-6, and surgical approach were independent predicators for patients undergoing interventions ≥3. A nomogram was built with area under ROC curve 0.891. Compared with step-up approach, one-step surgery was safe and effective in selected IPN patients with less interventions and shorter hospital stay. ? 2019 S. Karger AG, Basel.