Backgrounds: The relationship between Helicobacter pylori infection and symptoms remains controversial. We aimed to determine if an association exists between unexplained dyspepsia (pain or discomfort centered in the upper part of the abdomen) and H pylori. Methods: A validated questionnaire was completed by 592 healthy blood donors. Helicobacter pylori serologic values (via enzyme-linked immunosorbent assay), blood group status, and Rh status were measured; 4.9% of subjects who had a history of peptic ulcer disease were excluded from the analyses. Results: The prevalence of dyspepsia and no ulcer history was 11% (95% confidence interval [CI], 8.6%-13.8%); 15.4% of subjects with dyspepsia had H pylori while 14.6% of subjects without dyspepsia were infected (P = .90). The mean dyspepsia impact scores (combining frequency and severity) in those with and without H pylori were 4.7 and 5.4, respectively (P = .20). The median H pylori optical density values in dyspepsia vs no dyspepsia were not significantly different (P = .30). Independent risk factors for dyspepsia were the use of aspirin (odds ratio [OR], 2.2; 95% CI, 1.3-3.7) and smoking (OR, 2.1; 95% CI, 1.3-3.6) but not age, sex, marital status, educational level, income, or the use of alcohol, coffee, or nonsteroidal antiinflammatory drugs. Independent risk factors for H pylori were increasing age (OR, 1.8 per decade; 95% CI, 1.5- 2.3), male sex (OR, 2.1; 95% CI, 1.3-3.4), and net family income (OR, 1.8; 95% CI, 1.2-3.3). Conclusion: Dyspepsia in the community is linked to smoking and aspirin use, but not to H pylori infection.