P-selectin expression has been shown in Helicobacter pylori-infected persons, an infection that has been clinically associated with platelet-related diseases, such as idiopathic thrombocytopenic purpura. However, the role of P-selectin expression during H pylori infection remains unclear. In this study, we hypothesized that P-selectin expression was associated with platelet aggregation during H pylori infection. Using flow cytometry, we examined the levels of adhesion between H pylori and platelets as well as the levels of P-selectin expression and platelet phosphatidylserine (PS) expression during H pylori infection. Significantly high levels of adhesion between pro-aggregatory bacteria and platelets were observed. We identified that H pylori IgG is required for bacteria to induce P-selectin expression and that a significant release of P-selectin is essential for H pylori to induce aggregation. In addition, cellular apoptotic signs, such as membrane blebbing, were observed in platelet aggregates. PS expression was also detected in platelets during infection with both pro-aggrogatory and nonaggregatory strains of H pylori. These results suggest that the decrease in platelet counts seen during H pylori infection is the result of P-selection-dependent platelet aggregation and PS expression induced by the bacteria.