There are an estimated 250,000 heart valve replacement surgeries performed yearly on a worldwide basis. Mechanical prostheses have an excellent track record of durability (25 years or more), but current models require lifelong anticoagulation. Improved hemodynamics and reduced thrombogenicity characterize bioprosthetic valves; however, there is the disadvantage of degeneration, particularly in younger individuals. The ideal replacement—a tissue engineered “copy” of a native valve—is under development. The most feared and devastating complications of native or prosthetic valvular heart disease for patients, clinicians, and surgeons are valve thrombosis and systemic embolism. Although the incidence of thromboembolic events has decreased in North America in parallel with the reduced occurrence of rheumatic heart disease, this has not been the case in other parts of the world. Moreover, despite the improvements in design and surgical techniques, thromboembolism remains a serious complication of prosthetic heart valve replacement. The risk of thromboembolism in patients with native valvular heart disease is influenced strongly by the site of involvement, chamber dimension, ventricular performance, and presence of concomitant risk factors such as atrial fibrillation. Prior thromboembolism is considered a strong risk factor for recurrent events regardless of the valvular pathology. The risk of thromboembolism in patients with prosthetic valvular heart disease is recognized. Despite methodologic limitations, the available information derived from relatively large studies and an ever-expanding clinical experience allows several conclusions to be drawn: . . . • Thromboprophylaxis for mechanical prostheses is achieved most effectively with oral anticoagulants. . . . . . . • Antiplatelet therapy alone does not offer adequate protection for patients with mechanical prostheses. . . . . . . • The thrombogenicity of mechanical heart valves, from greatest to least, is as follows: caged ball > tilting disk > bileaflet. . . . . . . • High-risk patients (increased risk for thromboembolism) benefit from combination (anticoagulant and platelet antagonist) antithrombotic therapy. . . . . . . • A “threshold” level of anticoagulation is required for benefit. . . . . . . • High-intensity anticoagulation (international normalized ratio [INR] >3.5) increases the risk for hemorrhagic complications. . . . . . . • The risk of thromboembolism following bioprosthetic heart valve replacement is greatest during the first 3 postoperative months (Acar et al., 1996; Horstkotte et al., 1994; Sethia et al., 1986; Vogt et al., 1990). . . .