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Introduction Endoscopic submucosal dissection (ESD) is revolutionizing the field of endoscopy around the globe. Robot-assisted ESD is a novel technique that enables faster, safer, and more precise ESD, offering new hope to improve patients’ outcomes. This systematic review and meta-analysis provides the first comprehensive evidence evaluating of the safety and feasibility of robot-assisted ESD.Methods We conducted a comprehensive search of electronic databases, including MEDLINE via PubMed, Scopus, Web of Science, and Cochrane. No restrictions were applied on publication date or language. We included human studies only. Our primary outcomes were en bloc resection rates, the length of the procedure, recurrence rates, and complications like perforation and bleeding. We utilized R software 4.4.1 to perform the analysis.Results Eight studies consisting of two clinical trials, three cohort studies, and three case reports. In the 118 participants, there were 92 adenomas and 15 adenocarcinomas. The lesions located mainly at the colon and rectum except six lesions were gastric. The en bloc resection rate was 97.4%, 95% CI (0.901, 0.933), while the complete resection rate was 82.9%, 95% CI (0.722, 0.9). The mean procedure time was 82.03 min (95% CI: 48.13, 115.94). Regarding the safety outcomes, the intraoperative bleeding rate was 1.8%, 95% CI (0.004, 0.068), the recurrence rate of 2.6%, 95% CI (0.009, 0.006), and the perforation rate was 0.9 %, 95% CI (0.001, 0.060).Conclusion Our systematic review and meta-analysis demonstrated the efficacy and safety of robot-assisted endoscopic submucosal dissection in managing gastrointestinal neoplasms, especially in cases involving larger or more complex lesions that are challenging to manage with conventional ESD.References Fukami N. Endoscopic submucosal dissection in the esophagus. Gastrointestinal Endoscopy Clinics of North America, 2022;33(1):55–66. https://doi.org/10.1016/j.giec.2022.09.003Kim, Sang Hyun, et al. A novel retractable robotic device for colorectal endoscopic submucosal dissection. Gut And Liver, 2024;18(4):677–85. https://doi.org/10.5009/gnl230280.