BACKGROUND Although gastric cancer (GC) and duodenal ulcer (DU) are both strongly associated with Helicobacter pylori infection, a DU is negatively associated with the risk of GC. The aim of the study is to evaluate histologic risk factors for GC among patients with a DU. METHODS A total of 541 consecutive patients with GC were prospectively evaluated for the presence of a DU. Control patients with only a DU (n = 89) were recruited from health screening population. Histologic grading was assessed using the updated Sydney system for six gastric biopsies from three regions. GC risk among patients with a DU was evaluated using logistic regression analysis. RESULTS Among patients with GC, 7.6% (41/541) had a concomitant DU or an ulcer scar. Corpus-predominant/pangastritis were more frequently found in concomitant GC patients with a DU (90%) than in patients with a DU alone (62%) (p = .001). In patients with a DU, moderate-severe chronic inflammation at the lesser and greater curvatures of corpus was associated with GC risk (OR, 3.70; 95% CI, 1.46-9.36, and OR, 7.72; 95% CI, 3.18-18.7, respectively). Additionally, moderate-severe intestinal metaplasia (IM) at the antrum and corpus lesser curvature was associated with GC risk (OR, 7.52; 95% CI, 3.06-18.5, and OR, 9.25, 95% CI, 2.39-35.8, respectively). CONCLUSIONS A DU is not rare in patients with GC in a high-risk region of GC. Patients with a DU with chronic corpus gastritis and IM have an increased risk of GC, thus those patients should be followed up for GC development.