This chapter about treatment and prevention of stroke is part of the 7th 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). Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke (AIS), we recommend administration of IV tissue plasminogen activator (tPA), if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with extensive and clearly identifiable hypodensity on CT, we recommend against thrombolytic therapy (Grade 1B). For unselected patients with AIS of > 3 h but < 6 h, we suggest clinicians not use IV tPA (Grade 2A). For patients with AIS, we recommend against streptokinase (Grade 1A) and suggest clinicians not use full-dose anticoagulation with IV or subcutaneous heparins or heparinoids (Grade 2B). For patients with AIS who are not receiving thrombolysis, we recommend early aspirin therapy, 160 to 325 mg qd (Grade 1A). For AIS patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low molecular weight heparins or heparinoids (Grade 1A); and for patients who have contraindications to anticoagulants, we recommend use of intermittent pneumatic compression devices or elastic stockings (Grade 1C). In patients with acute intracerebral hematoma, we recommend the initial use of intermittent pneumatic compression (Grade 1C+). In patients with noncardioembolic stroke or transient ischemic attack (TIA) [ie, atherothrombotic, lacunar or cryptogenic], we recommend treatment with an antiplatelet agent (Grade 1A) including aspirin, 50 to 325 mg qd; the combination of aspirin and extended-release dipyridamole, 25 mg/200 mg bid; or clopidogrel, 75 mg qd. In these patients, we suggest use of the combination of aspirin and extended-release dipyridamole, 25/200 mg bid, over aspirin (Grade 2A) and clopidogrel over aspirin (Grade 2B). For patients who are allergic to aspirin, we recommend clopidogrel (Grade 1C+). In patients with atrial fibrillation and a recent stroke or TIA, we recommend long-term oral anticoagulation (target international normalized ratio, 2.5; range, 2.0 to 3.0) [Grade 1A]. In patients with venous sinus thrombosis, we recommend unfractionated heparin (Grade 1B) or low molecular weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase.