Helicobacter pylori infection is common in Iran as in other developing countries. Certain genotypes of H. pylori have been associated with increased occurrence of chronic gastritis, peptic ulcers, and gastric adenocarcinoma. The aim of this study was to investigate the clinical relevance of cagL gene and other virulence genotypes of H. pylori isolates with clinical outcomes in Iranian patients. Totally, 126 symptomatic patients who underwent gastroduodenal endoscopy were enrolled in the study. Sixty-one H. pylori strains were isolated from the patients studied. The presence of the cagL, cagA, vacA, iceA, babA2 and sabA genes in the corresponding H. pylori isolates were determined by polymerase chain reaction and the results were compared with clinical outcomes and histopathology. The cagL, cagA, vacA s1, vacA s2, vacA m1, vacA m2, iceA1, iceA2, babA 2 , and sabA genotypes were detected in 96.7, 85.2, 75.4, 24.6, 29.5, 70.5, 42.6, 23, 96.7, and 83.6 of the isolates, respectively. The three genotypic combinations, cagL/cagA/vacAs1m1/iceA1/babA2/sabA, cagL/cagA/vacAs1m2/iceA1/babA2/sabA, and cagL/cagA/vacAs1m2/iceA2/babA2/sabA were determined as the most prevalent combined genotypes. There was a significant correlation between the presence of cagL gene and cagA positivity (P = 0.02). No significant correlation was found between the various genotypes and clinical outcomes (P > 0.05). The present study showed a very high prevalence of cagL genotype among the H. pylori isolates from Iranian patients. Our results demonstrated that neither single genotype nor combination genotypes of virulence-associated genes was significantly helpful markers for predicting the severity of gastroduodenal disease associated with H. pylori infection in Iranian patients.