This chapter about antithrombotic therapy for acute myocardial infarction (MI) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients’ values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S–187S). Among the key recommendations in this chapter are the following: For patients with ischemic symptoms characteristic of acute MI of < 12 h in duration, and ST-segment elevation or left bundle-branch block (of unknown duration) on the ECG, we recommend administration of any approved fibrinolytic agent (Grade 1A). We recommend the use of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over placebo (all Grade 1A). For patients with symptom duration < 6 h, we recommend the administration of alteplase over streptokinase (Grade 1A). For patients with known allergy or sensitivity to streptokinase, we recommend alteplase, reteplase, or tenecteplase (Grade 1A). For patients with acute posterior MI of < 12 h duration, we suggest fibrinolytic therapy (Grade 2C). In patients with any history of intracranial hemorrhage, closed head trauma, or ischemic stroke within past 3 months, we recommend against administration of fibrinolytic therapy (Grade 1C+). For patients with acute ST-segment elevation MI whether or not they receive fibrinolytic therapy, we recommend aspirin, 160 to 325 mg po, at initial evaluation by health-care personnel followed by indefinite therapy, 75 to 162 mg/d po (both Grade 1A). In patients allergic to aspirin, we suggest use of clopidogrel as an alternative therapy to aspirin (Grade 2C). For patients receiving streptokinase, we suggest administration of either IV unfractionated heparin (UFH) [Grade 2C] or subcutaneous UFH (Grade 2A). For all patients at high risk of systemic or venous thromboembolism (anterior MI, pump failure, previous embolus, atrial fibrillation, or left ventricular thrombus), we recommend administration of IV UFH while receiving streptokinase (Grade 1C+).