Debridement of infected walled-off pancreatic necrosis is indicated to treat and prevent sepsis-related multiorgan failure. The aim of this study was to evaluate the efficacy and safety of the EndoRotor-powered endoscopic debridement system to remove solid debris under direct endoscopic visualization. Search strategies were developed for PubMed, EMBASE, and Cochrane Library databases from inception to June 2022, in accordance with Preferred Reporting items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Outcomes of interest included technical success defined as successful use of device for debridement, clinical success defined as complete debridement and cyst resolution, and procedure-related adverse events. A random-effects model was used for analysis, and results were expressed as odds ratio along with 95% confidence interval. A total of 7 studies (n = 79 patients) were included. The mean walled-off pancreatic necrosis size was 154.6 ± 34.0 mm, whereas the mean procedure time was 71.4 minutes. The mean number of necrosectomy sessions required was 2.2 (range, 1–7). The pooled rate of clinical success was 96% (95% confidence interval, 91%–100%; I
2 = 0%) with a pooled technical success rate of 96% (91%–100%; I
2 = 0%). The pooled procedure-related adverse event rate was 8% (2%–14%; I
2 = 6%), which included procedure-associated bleeding, pneumoperitoneum, peritonitis, pleural effusion, and dislodgement of lumen-apposing metal stents. Our study shows that the novel EndoRotor device seems to be safe and effective for treating pancreatic necrosis. Patients undergoing endoscopic necrosectomy with the EndoRotor seem to require less debridement sessions when compared with studies using conventional instruments.