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Background and study aims Endoscopic resection has traditionally involved electrosurgical cautery (hot snare) to resect premalignant polyps. Recent data have suggested superior safety of cold resection. We aimed to assess the safety of cold compared with traditional (hot) resection for non-ampullary duodenal polyps. Methods We performed a systematic review ending in September 2022. The primary outcome of interest was the adverse event (AE) rate for cold compared with hot polyp resection. We reported odds ratios with 95% confidence intervals (CIs). Secondary outcomes included rates of polyp recurrence and post-polypectomy syndrome. We assessed publication bias with the classic fail-safe test and used forest plots to report pooled effect estimates. We assessed heterogeneity using I 2 index. Results Our systematic review identified 1,215 unique citations. Eight of these met inclusion criteria, seven of which were published manuscripts and one of which was a recent meeting abstract. On random effect modeling, cold resection was associated with significantly lower odds of delayed bleeding compared with hot resection. The difference in the odds of perforation (odds ratio [OR] 0.31 [95% confidence interval [CI] 0.05-2.87], P =0.2, I 2 =0) and polyp recurrence (OR 0.75 [95% CI 0.15-3.73], P =0.72, I 2 =0) between hot and cold resection was not statistically significant. There were no cases of post-polypectomy syndrome reported with either hot or cold techniques. Conclusions Cold resection is associated with lower odds of delayed bleeding compared with hot resection for duodenal tumors. There was a trend toward higher odds of perforation and recurrence following hot resection, but this trend was not statistically significant., Competing Interests: Conflict of Interest Dr. Qumseya is a consultant for Medtronic, Assertio Management, and Endogastric Solutions, and is a speaker for Castle Biosciences. All of the other authors confirm that they have no conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)