Stents represent a thrombogenic surface where one of the earliest events is the deposition of platelets. Activated platelets express neoepitopes that enable them to form homo- and heterotypic aggregates and activate the coagulation system. In this study, we investigated the effects of ad hoc clopidogrel treatment compared to a clopidogrel pretreated group on platelet P-selectin expression. We found that after stent implantation in the ad hoc treated group, P-selectin expression decreased after 1 h, while the initial decrease in platelet count normalized after 4 h. Aspirin non-responsiveness did not influence the results. These data point to the beneficial effect of clopidogrel treatment in reducing platelet reactivity during stenting.