Acute coronary syndromes (ACS) are one of the most dramatic manifestations of atherothrombosis and several efforts have been made in recent years to improve their prognosis. Morbidity and mortality of high-to-medium risk ACS have significantly reduced in the real world setting during the last few years, due to a very aggressive antithrombotic therapy, which always involves a combination of an anticoagulant and different antiplatelet agents, and an extensive indication to revascularization. However, it has become increasingly important for clinicians to identify the correct treatment between the several different combination of antithrombotic and antiplatelet agents. The selection and intensity of these combinations are based in the first instance on the ischemic risk profile of the patient and the treatment strategy (early invasive, delayed invasive or conservative) selected. However, the use of such an aggressive antithrombotic therapy coupled with coronary angioplasty exposes the patients to a significant risk of bleeding. Unfortunately, these bleeding complications have a negative prognostic significance and force clinicians to suspend (or decrease) the antithrombotic treatments to control bleeding.