The introduction of clopidogrel for use with aspirin (ASA) as a dual antiplatelet therapy has markedly reduced the risk of atherothrombotic vessel occlusion in patients with acute coronary syndromes (ACS). However, stronger antiplatelet therapy has also been associated with significant increases in severe bleeding, resulting in no change in mortality rates. This raised the question of pharmacological alternatives, specifically new antagonists of the platelet P2Y(12)-ADP receptor, which exhibit better pharmacokinetic and dynamic properties than clopidogrel, as well as improved clinical safety.Prasugrel, the first of these newly developed agents and another thienopyridine, was more potent than clopidogrel in the TRITON-TIMI-38 study in reducing ischemic events in ACS patients, but also increased severe bleeding. Ticagrelor, a structurally different reversible antagonist of the P2Y(12) receptor, was superior to clopidogrel in the PLATO trial on ACS patients, but also increased the risk of severe bleeding in patients not requiring bypass surgery. Interestingly, ticagrelor reduced mortality in PLATO. There have been no satisfying explanations for this phenomenon to date. In addition to different patient populations and treatment protocols, the varying pharmacological properties of these substances are discussed as possible causes. A direct comparison of the two medications in a single study remains to be undertaken.