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Background and Aim: Developments of endoscopic techniques brought the possibility of endoscopic resection for gastrointestinal stromal tumors (GISTs) of larger sizes. We aim to compare safety and short‐term outcomes between endoscopic and laparoscopic resections of gastric GISTs with a diameter of 2–5 cm. Methods: This is a single‐center, retrospective cohort study. The clinical data, perioperative conditions, and the adverse events of patients who underwent endoscopic or laparoscopic resection for gastric GIST of 2–5 cm in Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were retrospectively reviewed. Results: A total of 346 patients were reviewed; 12 patients who failed to accomplish the planned procedure were excluded; 182 underwent laparoscopic resection; and 152 underwent endoscopic resection. Significant differences exist in the tumor size between the laparoscopic group (3.43 ± 0.86 cm) and the endoscopic group (2.78 ± 0.73 cm) (P < 0.01). Compared with laparoscopic resection, endoscopic resection was associated with faster recovery (P < 0.01), shorter hospital stays (P < 0.01), and lower cost (P < 0.01). The incidence of Clavien–Dindo grade II–V adverse events in the endoscopic group (3/152) was significantly lower than that in the laparoscopic group (12/182) (P = 0.04). After a propensity score matching analysis, the endoscopic group showed similar incidences of complications with the laparoscopic group, while the advantages over laparoscopic resection in postoperative hospital stay, time to first oral intake, and hospitalization expenses remained significant (P < 0.01). Conclusions: Endoscopic resection is a safe and cost‐effective method for 2–5 cm of gastric GISTs compared with laparoscopic resection. [ABSTRACT FROM AUTHOR]