BackgroundEndoscopic resection (ER) is a promising technique for resecting gastric gastrointestinal stromal tumors (gGISTs); however, ER is technically challenging. This study aimed to develop and validate a difficulty scoring system (DSS) to determine the difficulty for ER of a gGIST.MethodsThis retrospective study enrolled 555 patients with gGISTs in multi-centers from December 2010 to December 2022. Data on patients, lesions, and outcomes of ER were collected and analyzed. Adifficult casewas defined as an operative time ≥ 90 min, or the occurrence of severe intraoperative bleeding, or conversion to laparoscopic resection. The DSS was developed in the training cohort (TC) and validated in the internal validation cohort (IVC) and external validation cohort (EVC).ResultsThe difficulty occurred in 97 cases (17.5%). The DSS comprised the following: tumor size ≥ 3.0 cm (3 points) or 2.0–3.0 cm (1 point); location in the upper third of the stomach (2 points); invasion depth beyond the muscularis propria (2 points); lack of experience (1 point). The area under the curve (AUC) of DSS in IVC and EVC was 0.838 and 0.864, respectively, and the negative predictive value (NPV) was 0.923 and 0.972, respectively. The proportions of difficult operation in easy (score 0–3), intermediate (score 4–5), and difficult (score 6–8) categories were 6.5%, 29.4%, and 88.2% in the TC, 7.7%, 45.8%, and 85.7% in the IVC, and 7.0%, 29.4%, and 85.7% in the EVC, respectively.ConclusionsWe developed and validated a preoperative DSS for ER of gGISTs based on tumor size, location, invasion depth, and endoscopists’ experience. This DSS can be used to grade the technical difficulty before surgery.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00464-023-10106-w.