Permanent therapy with oral anticoagulants offers the most consistent protection in patients with mechanical heart valves. Antiplatelet agents alone do not consistently protect patients with mechanical prosthetic heart valves, including patients in sinus rhythm with St. Jude valves in the aortic position. Levels of oral anticoagulants that prolong the INR to 2.0 to 3.0 appear satisfactory for patients with bileaflet mechanical valves in the aortic position, provided they are in sinus rhythm and the left atrium is not enlarged. Oral anticoagulant levels that prolong the INR to 2.5 to 3.2 are satisfactory for patients with bileaflet mechanical aortic valves and atrial fibrillation. Oral anticoagulant levels that prolong the INR to 2.5 to 3.5 are satisfactory for tilting disk valves and bileaflet prosthetic valves in the mitral position. Experience is sparse in patients with caged ball valves who had prothrombin time ratios reported in terms of INR. It has been suggested that the most advantageous INR level in patients with caged ball or caged disk valves should be as high as 4.0 to 4.9. However, others have shown a high rate of major hemorrhage with an INR that is even somewhat lower (3.0 to 4.5). The problem is self-limited, however, because few such valves are being inserted. Aspirin, in addition to oral anticoagulants, in patients with mechanical heart valves has been shown to diminish the frequency of thromboemboli. The risk of bleeding may not be increased if the INR is low. A low rate of both thromboemboli and bleeding has been shown with an INR of 2.5 to 3.5 in combination with aspirin at a dose of 100 mg/d. There are no investigations in which an aspirin dose of 81 mg/d in combination with oral anticoagulants was evaluated. Dipyripdamole may be effective in reducing the rate of thromboemboli without increasing the rate of bleeding, but data are insufficient to recommend dipyridamole over low doses of aspirin. Patients with bioprosthetic valves in the mitral position, as well as patients with bioprosthetic valves in the aortic position, may be at risk for thromboemboli during the first 3 months after surgery. Among patients during the first 3 months after surgery with bioprosthetic valves in the mitral position, oral anticoagulants administered at an INR of 2.0 to 2.3 were as effective as at an INR of 2.5 to 4.5: additionally, fewer bleeding complications were seen.