Introduction: Endoscopic mucosal resection (EMR) is utilized for removing preneoplastic or neoplastic lesions from the gastrointestinal tract. EMR is recommended for patients with a high risk of mucosal cancer, but the use of various thermal ablation techniques is associated with post-therapeutic stenosis. EndoRotor is a non-thermal device that suctions target epithelium into a small catheter where a spinning knife resects the mucosa, which reduces the risk of scarring and stenosis. Therefore, we performed a systematic review and meta-analysis to evaluate the safety of EndoRotor for non-thermal ablation of Barrett’s esophagus. Methods: A systematic review of the literature was performed using Medline, Embase, Web of Science, and the Cochrane library database until June 2022 to identify all studies that evaluated the safety of non-thermal endoscopic resection devices for the ablation of Barrett's esophagus. Other outcomes of interest included rates of intraoperative bleeding, post-procedural bleeding, perforation, post-procedural stenosis, and post-procedural pain or discomfort. All analyses were conducted using comprehensive meta-analysis software. Results: Five studies, including 70 patients, were included in the final analysis. There were four observational studies and one randomized controlled trial. The pooled rate of intraoperative bleeding was 39% (95% CI: 25.4-54.5%, I2=0) and post-procedural bleeding was 7.5% (95% CI: 2.6%-19.6%, I2=0). The pooled rate of perforation was 4.1% (1.3%-11.9%, I2=0), post-procedural follow-up stenosis was 11.2% (4.7%-24.2%, I2=0), and post-procedural pain or discomfort was 54.2% (95% CI: 41.5%-66.4%, I2=9.2%). The efficacy of EndoRotor was not evaluated given the lack of data reported in the included studies. Conclusion: The new EndoRotor resection device could be a viable alternative to existing ablative therapies for Barrett's esophagus. However, our study revealed significant adverse events, and therefore, larger randomized control trials are warranted to evaluate the risks and benefits of this novel device.