Thienopyridine antiplatelet drugs have been used for 15 years for the prevention of coronary stent thrombosis in patients undergoing percutaneous coronary intervention with stent placement. Ticlopidine, the first approved thienopyridine, has in large part been replaced by clopidogrel, a more potent and better tolerated thienopyridine. Now, prasugrel, the newest agent, is currently available for use in the United States. Although prasugrel is similar to clopidogrel, it is about 10 times more potent and has a quicker onset of action. Data from the largest trial comparing clopidogrel and prasugrel indicate that this increased potency and quicker onset of prasugrel equate to a reduction in major adverse cardiovascular events, although higher rates of major bleeding were reported. Prasugrel also differs from clopidogrel in that it may be less prone to drug-drug interactions and patient nonresponsiveness, although further research is needed in both of these areas. Given the totality of data available, prasugrel appears to be a promising treatment option for patients with acute coronary syndromes who are undergoing percutaneous coronary interventions.