Factors affecting Helicobacter pylori eradication rate with omeprazole (OME), clarithromycin (CL), and amoxicillin (AMO) have not been extensively studied. We have investigated the effect of age, sex, smoking, ulcer disease, compliance with therapy, H. pylori colonization density, degree and activity of antral gastritis, the coexistence of corpus gastritis, and the presence of lymphoid follicles on H. pylori eradication rate. We studied 80 consecutive H. pylori-positive patients, with duodenal ulcer (N = 35) or nonulcer dyspepsia (N = 45) treated with OME 20 mg, CL 500 mg, and AMO 1 g, each given twice daily for 10 days. H. pylori was eradicated in 71/80 (88.8%, 95% CI 82–96%) patients. The regimen failed to eradicate the only strain (1.8%, 95% CI 0–5.2%) that was clarithromycin resistant. Multivariate discriminant analysis showed that two histological variables (Wilks λ = 0.74, χ² = 23.41, df = 2, P < 0.001), absence of lymphoid follicles in routine gastric biopsies (F = 13.63, P < 0.001) and coexistence of antral and body gastritis (F = 13.68, P < 0.001), significantly increased H. pylori eradication rate. No other factor examined predicted H. pylori eradication with this regimen. Our data suggest that body gastritis is a positive and presence of lymphoid follicles in routine gastric biopsies is a negative predictive factor of treatment outcome with the omeprazole, clarithromycin, and amoxicillin regime.