The term “hypercoagulability” is used to describe patients who are at increased risk for thrombosis because of inherited defects in their anticoagulant pathways or because of various predisposing causes. About one in five patients of European descent who present with venous thromboembolism have a specific genetic defect in their anticoagulant pathway. In these patients, anticoagulant prophylaxis is indicated at times of high risk, such as after surgery. Prolonged anticoagulant therapy may be required in patients with recurrent or life-threatening thromboemboli, but decisions about this are best made on an individual basis. Patients who present with arterial thrombosis usually develop their disease as a complication of atherosclerosis. However, these patients also have a form of hypercoagulability, manifested primarily by high fibrinogen levels and elevated factor VII activity. Evidence increasingly indicates that these and other hemostatic markers may help in the assessment of patients at risk for coronary heart disease.