OBJECTIVES: Endoscopic full-thickness resection for gastric submucosal tumors is gradually gaining popularity, and secure and amenable closure is key to its success. This study aimed to compare the reopenable clip over-the-line method with the purse-string method for defect closure after endoscopic full-thickness resection for gastric submucosal tumors. METHODS: This historical control trial included 37 consecutive patients with 37 gastric submucosal tumors, who underwent endoscopic full-thickness resection between January 2021 and July 2024. All lesions were resected en bloc. After excluding three patients who underwent non-full-thickness resection, 34 patients were analyzed. Post-endoscopic full-thickness resection defects were closed using the purse-string method ( RESULTS: The median (interquartile range) time for defect closure was longer in the reopenable clip over-the-line method group of 33 (31-57) min than in the purse-string method group of 26 (24-35) min ( CONCLUSIONS: Reopenable clip over-the-line method facilitated secure post-endoscopic full-thickness resection defect closure, reduced post-procedural abdominal pain, and shortened the fasting and hospitalization periods after endoscopic full-thickness resection in gastric submucosal tumors.