Inhibition of blood coagulation is an essential cornerstone of the therapy of acute myocardial infarction. Risk stratification represents a valuable tool to adjust the intensity of anticoagulation and timing of invasive therapy according to patient risk. All patients presenting with myocardial infarction should be treated with aspirin and clopidogrel. Patients with ST-segment elevation myocardial infarction and high-risk patients with myocardial infarction without ST-segment elevation who undergo invasive therapy should be treated immediately with unfractionated heparin (alternatively enoxaparin) and a glycoprotein (GP) IIb/IIIa antagonist in the catheter laboratory. The direct thrombin antagonist bivalirudin may emerge as an attractive alternative in these patients. In low-risk patients who undergo delayed urgent elective interventional therapy the factor Xa antagonist fondaparinux may be advantageous because of its low bleeding rate. In these patients administration of unfractionated heparin is necessary for percutaneous coronary intervention.