ObjectiveTo compare the efficacy and safety of endoscopic submucosal excavation (ESE) and endoscopic full-thickness resection (EFR) for intraluminal gastric stromal tumors. MethodsData of 441 patients diagnosed as having gastric stromal tumors in Nanjing Drum Tower Hospital from June 2009 to June 2020 were retrospectively analyzed. A total of 241 patients underwent ESE (ESE group) and 200 EFR (EFR group). Epidemiological data (gender, age and body mass index), tumor size, procedure related parameters, complications, hospital stay, cost and follow-up were compared between the two groups. ResultsThere were no significant differences between the two groups in gender, age, body mass index, tumor size, National Institutes of Health risk grade, complete resection rate, or block resection rate (P>0.05). Compared with the EFR group, the ESE group required less titanium clips to close defects in the stomach wall [6.0 (4.0, 6.0) VS 6.0 (5.0, 8.0), U=18 424.0. P<0.001], shorter time of first postoperative fluid intake [2.0 (1.0, 2.0) days VS 2.0 (2.0, 3.0) days, U=17 420.0, P<0.001] and hospital stay [6.0 (5.0, 8.0) days VS 7.0 (6.0, 9.0) days, U=18 906.0, P<0.001], and lower total cost [18.9 (16.4, 21.4) thousand yuan VS 20.9 (18.1, 23.8) thousand yuan, U=17 956.0, P<0.001]. Moreover, the total incidence of complications of the ESE group was lower than that of the EFR group [5.8% (14/241) VS 11.5% (23/200), χ2=4.605, P=0.032]. Patients were followed up with the median period of 45.0 months. The disease recurrence rate was 0.45% (2/441), and there were no disease-related deaths. ConclusionThe efficacy is comparable between ESE and EFR for treating intraluminal gastric stromal tumors, but ESE shows a lower incidence of complications, and requires a shorter hospital stay and lower cost.