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Clopidogrel has decreased the rate of thrombotic events in patients undergoing percutaneous coronary intervention. However, two major limitations of the drug have been involved in the persistence of a relatively high rate of adverse events. The recent literature suggested that improved platelet reactivity inhibition using a higher or tailored dose of clopidogrel, or a more potent agent, could reduce the rate of events. The development of new antiplatelet agents and the increasing availability of platelet assays are likely to profoundly modify current practice and favor personalized antiplatelet therapy.