BACKGROUND/AIMS: Epidemiological data indicate that emotional stress and depression might influence the development of gastrointestianl disorders and cancers, but the relationship between the two is still unclear. The aim was to investigate the effect of stress/depression on the prevalence of digestive diseases. In addition, we tried to identify whether stress and depression are risk factors for these diseases. METHODS: A total of 23 698 subjects who underwent a medical check-up including upper and lower endoscopy were enrolled. By review -ing the subject's self-reporting questionnaire and endoscopic findings, we investigated the digestive diseases, including functional dyspepsia (FD), irritable bowel syndrome (IBS), reflux esophagitis, peptic ulcer disease, and adenoma and carcinoma of the stomach and colon. Stress and depression scores were measured by the Brief Encounter Psychosocial Instrument and Beck's Depression Inventory, respectively (Korean version). RESULTS: Stress and depression were related to FD, IBS, and reflux esophagitis. Depression was also linked to peptic ulcer disease and adenoma/carcinoma of the colon and stomach. Multivariate analysis revealed that stress and depression were independent risk factors for FD (OR, 1.713 and 1.984; P < 0.001) and IBS (OR, 1.730 and 3.508; P < 0.001). In addition, depression was an independent risk factor for gastric adenoma/carcinoma (OR, 4.543; P < 0.001). CONCLUSIONS: Stress and depression are related to various digestive diseases, and they may be predisposing factors for FD and IBS. Depression may also be a cause of gastric cancer. Psychological evaluation of gastroenterology patients may be necessary, but more study is needed.