this study was aimed to explore the bidirectional association between depression and peptic ulcers. the ≥20-year-old participants of the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013 were included in the study. In study I, 30,306 depression patients were 1:4 matched with 121,224 control I participants. In study II, 127,590 peptic ulcer patients were 1:1 matched with 127,590 control II participants. The stratified Cox-proportional hazards models were used to analyse the hazard ratio (HR) of depression for peptic ulcers (study I) and of peptic ulcers for depression (study II). A total of 8.9% (2,703/ 30,306) of depression patients and 7.3% (8,896/ 121,224) of patients in the control I group had peptic ulcers (P < 0.001). The depression group had an adjusted HR for peptic ulcers that was 1.14-fold higher than that of the control I group (95% confidence interval [95% CI] = 1.09-1.19, p < 0.001). A total of 6.4% (8,144/ 127,590) of peptic ulcer patients and 3.5% (4,515/127,590) of patients in the control II group had depression (P < 0.001). The peptic ulcer group had an adjusted HR for depression that was 1.68-fold higher than that of the control II group (95% CI = 1.62-1.74, P < 0.001). Depression and peptic ulcers exhibited a bidirectional relationship. Depression is a prevalent psychological disease worldwide. A meta-analysis reported an approximately 27.0% prevalence of depressive symptoms in 83 cross-sectional studies (95% confidence intervals [95% CIs] = 24.0-29.0) 1. In Korea, about 6.7% of all age population suffered from depression (95% CI = 5.7-7.6) 2. Depression increases the risk of several physical illnesses, such as cardiovascular disease, stroke, and diabetes 3. The disturbances of metabolism, immune-inflammatory responses, autonomic regulation, and hypothalamic-pituitary-adrenal-axis in depression patients were suggested to be linked with the elevated risk of chronic diseases 3. In line with this idea, depression was reported to increase the risk of a number of gastrointestinal diseases 4,5. Several prior studies suggested a relationship between depression or psychological stress and gastrointestinal diseases 4,5. For instance, reflux oesophagitis was related to stress (odds ratio = 1.94, 95% CI = 1.25-3.02) 4. Peptic ulcer disease is defined as a submucosal injury in the digestive tract, mainly in the stomach and proximal duodenum 6. The prevalence of peptic ulcer disease is approximately 5-10%, with a decreasing tendency worldwide due to a attenuation of Helicobacter pylori infection and anti-acid medications 7,8. In Korea, approximately 5.6% of the adult population has peptic ulcer disease 9. In addition to H. pylori infection and the chronic nonsteroidal anti-inflammatory drug medications, the possible pathophysiological causes of peptic ulcer disease include the hypersecretion of acidic contents, dietary factors, and stress 6. Peptic ulcers have been associated with psychological stress, schizophrenia and anxiety 10-12. Peptic ulcer patients showed higher odds f...