Background/Aims: Few studies have compared the performances of endoscopic knives. This study aimed to compare the therapeutic outcomes of a novel core knife and the conventional IT knife 2 for endoscopic submucosal dissection (ESD) of gastric mucosal lesions.Methods: This prospective, non-inferiority trial included patients diagnosed with gastric adenoma or early-stage adenocarcinoma at Keimyung University Dongsan Hospital between June and November 2020. The patients were randomly assigned to either the core knife or the IT knife 2 group. The operators and assistants scored the knives’ grip convenience and cutting abilities.Results: A total of 39 patients were enrolled (core knife group, 20 patients; IT knife 2 group, 19 patients). There were no significant between-group differences in operator-assessed grip convenience (9.600 vs. 9.526, p=0.753), cutting ability (9.600 vs. 9.105, p=0.158), or assistant-assessed grip convenience (9.500 vs. 9.368, p=0.574).Conclusions: The core knife achieved therapeutic outcomes that were comparable to those of the IT knife 2 for ESD of gastric mucosal lesions.