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Background: Helicobacter pylori infection is a basic risk factor for chronic gastritis, and gastric carcinoma. Based on some studies, the reason is binding of H. pylori to H and Leb antigens in gastric mucosa. However, some other findings have not determined any association between the infection and these antigens. Because of this controversy and the fact that H. pylori infection and gastric adenocarcinoma are common diseases in Iran, the assessment of the association of H. pylori infection with these blood groups could be valuable. Materials and Methods: In a cross sectional study on 135 adult dyspeptic patients in Mashhad, Iran, from 2009 to 2010, H. pylori infection was evaluated by using the Heliprobe 14C‑urea breath test and the ABO and Lewis blood group antigens were determined by the tube method. Association between the Lewis and ABO phenotypes with H. pylori infection were analysed by Fisher’s exact test. A P ≤ 0.05 was considered to be significant. Results: 68 (50.4%) patients were positive for H. pylori infection. The frequencies of the ABO, Lewis and secretion phenotypes were not significant in the infected and non‑infected patients. We also did not find a significant association between Lea and Leb antigens and this infection. Conclusion: We could not establish a significant association between the Lewis, ABO and secretion phenotypes with H. pylori infection. Diversity of sequences of blood group antigen b‑binding adhesion (babA gene) of H. pylori may be a reason why our findings are different from other studies in other geographic areas.Keywords: ABO blood groups, gastritis, Helicobacter pylori, Lewis blood group, secretor blood groupNigerian Medical Journal | Vol. 54 | Issue 3 | May-June | 2013