Background and Objective: Helicobacter pylori has several strains with different degrees of virulence. The aim of this study was to detect two major important virulence factors, cagA/vacA genotypes, and to determine correlations among different cagA/vacA genotypes and histological features of chronic gastritis in Iranian patients. Methods: In this cross- sectional study, Gastric biopsy was taken from 166 patients with non-ulcer dyspepsia. The specimens were processed for DNA extraction and identificationof glmM gene. The vacA subtypes and cagA gene were tested by PCR. Histopathological features were recorded and graded according to updatedSydney system. Results: 76.7% of the H. pylori strains were cagA gene positive. The proportions of vacA gene subtypes s1, s2, m1 and m2 in the 78 strains isolated were 70.5%, 29.5%, 37.2% and 62.8%, respectively. 83.3% of the vacA-positive strains had s1 allele. Twenty-six strains (33.3%) were positive for both cagA and m1 allele. Positive cagA status and vacA subtypes were not associated significantly with presence of neutrophil infiltration, intestinal metaplasia or H. pylori density. Only vacA s1 was significantly associated with more severe inflammation (P=0.02).The dominant genotype of H. pylori was vacA+ s1/m2. CagA gene positivity rate was not closely associated with severity of the disease. Conclusion: H. pylori strains showing vacA s1 genotype were associated with more severe gastritis. These findings show that vacA genotyping may have clinical relevance in Iran.