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This study aimed to evaluate the psychological distress and associated risk factors for distress among patients with gastric epithelial neoplasm undergoing endoscopic submucosal dissection (ESD).A total of 91 patients treated with ESD for gastric epithelial neoplasm between May 2015 and June 2016 were prospectively enrolled. Sociodemographic factors, psychological distress, anxiety, depression, stress, and associated risk factors for psychological distress were evaluated the day before ESD.Twenty-six (28.6%) patients were identified as patients with psychological distress. The psychological distress group had a higher female ratio and more depression and anxiety symptoms than the non-distress group. Distress was also related to stress level. A multivariate analysis showed that unmarried status (odds ratio [OR], 4.94; 95% confidence interval [CI], 1.13–21.56, P = .034), anxiety (OR, 1.24; 95% CI, 1.12–1.39, P <.001), and stress (OR, 1.06; 95% CI, 1.01–1.12, P = .011) were associated with psychological distress.An unmarried status and a high level of anxiety and stress were associated with more psychological distress in patients undergoing gastric ESD. It could be helpful to screen and proactively monitor patients with such conditions before performing gastric ESD.