Background: The clinical result severity of Helicobacter pylori infection is determined by a combination of environmental factors, host genetic background, and H. pylori virulence factors. A number of genes containing vacA, iceA, babA2, cagA, cagE, hsp60-70, and hpa have been identified to enhance H. pylori pathogenicity by encoding virulent proteins. The babA and hpa proteins are considered 2 major adhesion molecules, and thus they are key agents in the initial step of H. pylori invasion. Objectives: This study aimed at investigating the existence of babA2 and hpa virulence factors of H. pylori in Iranian patients with gastrointestinal complications. The relationship between these agents and clinical results was also investigated. Methods: A total of 80 positive biopsies out of 156 samples were studied to determine babA2 and hpa gene frequency by PCR. The positive biopsies were collected from patients suffering from gastric cancer (n =18), peptic ulcer (n = 26), and gastritis (n =36). Results:The babA2+ strains were found in 51 (64%) patients and the hpa+ strains in 57 (71%) patients were associated with sex (P = 0.02). However, the frequency of these factors was not significant between gastric disease groups (P > 0.05). Conclusions: Our results revealed different frequency of these virulence factors in Iran, which emphasized the effects of geographical influences. Also, it was found that male patients had higher rate of hpa than females, highlighting the gender specific factors.