Helicobacter pylori genomes contain about 30 hop genes that encode outer membrane proteins. Helicobacter pylori hopQ alleles exhibit a high level of genetic diversity, and two families of hopQ alleles have been described. Type I hopQ alleles are found more commonly in cag-positive H. pylori strains from patients with peptic ulcer disease than in cag-negative strains from patients without ulcer disease. In this study, we mutated hopQ in four H. pylori strains that each contained a type I hopQ allele, and then analyzed interactions of the wild-type and hopQ mutant strains with AGS cells. In comparison with the wild-type strains, two of the hopQ mutant strains exhibited increased adherence to AGS cells and two hopQ mutants did not exhibit any detectable differences in adherence. Higher levels of tyrosine-phosphorylated CagA were detected when AGS cells were cocultured with a hyperadherent hopQ mutant strain than when cocultured with the corresponding wild-type strain. These data indicate that in some strains of H. pylori, the HopQ protein can attenuate bacterial adherence to gastric epithelial cells.