The risks of bleeding and thrombosis should be considered in decisions on whether to initiate anticoagulation therapy. Oral anticoagulation is indicated for patients with nonvalvular atrial fibrillation who are at intermediate or high risk of stroke (CHADS2 [Congestive heart failure, Hypertension, Age at least 75 years, Diabetes, previous Stroke or transient ischemic attack] score of 1 or higher). Apixaban, dabigatran, rivaroxaban, or warfarin can be considered for the prevention of stroke and systemic embolism in these patients. Hospitalized patients at high risk of thrombosis should receive prophylaxis with low-molecular-weight heparin, low-dose unfractionated heparin, or fondaparinux, whereas those at low risk should not receive pharmacologic prophylaxis. Pharmacologic prophylaxis with low-molecular-weight heparin or low-dose unfractionated heparin is indicated for patients undergoing nonorthopedic surgery who are at high risk of thrombosis and those undergoing orthopedic surgery whose risk of bleeding is low. Patients presenting with acute coronary syndrome should receive intravenous unfractionated heparin or enoxaparin at hospital admission. Anticoagulation with warfarin is appropriate for patients with mechanical heart valves. Patients with deep venous thrombosis or pulmonary embolism should receive rivaroxaban, dabigatran, or warfarin.