The main cause of the hemostasis defects and related bleeding complications in patients with acute coronary syndromes (ACS) are the intake of multiple antithrombotic drugs, alone or concomitantly with invasive procedures such as coronary angiography and percutaneous coronary intervention (PCI). Antithrombotic drugs that impair several phases of hemostasis (platelet function, coagulation, and fibrinolysis) are causing bleeding particularly in elderly patients, in those underweight and with comorbidities such as renal insufficiency, diabetes, hypertension and malignancy. Identification of patients at high risk of bleeding is the most important preventive strategy, because the choice and dosages of drugs may to some extent be tailored to the degree of risk. Transfusions of blood products, which may become necessary in patients with major bleeding, should be used with caution, because they are associated with adverse cardiovascular events. To reduce the need of transfusion, the hemostatic drugs that decrease blood loss and transfusion requirements in cardiac surgery (antifibrinolytic amino acids, desmopressin, and recombinant factor VIIa) might be considered. However, the efficacy of these drugs in the control of bleeding complications is not unequivocally established in ACS and there is concern for an increased risk of thrombosis. In conclusion, evidence-based recommendations for the management of bleeding in patients with ACS are currently lacking, so that prevention through accurate assessment of the individual risk is the most valid strategy.