Prosthetic heart valves have been effectively used for many years. Nonetheless, they are associated with risks of thrombosis and thromboembolic events, as well as anticoagulation-induced bleeding. Substantial changes in anticoagulation measurement and dosing have occurred during the past several years. In this review, the rationale for anticoagulation in patients with prosthetic heart valves, the changes in monitoring and dosing, and the comparison of relevant anticoagulation trials are discussed. On the basis of the existing data, new recommendations regarding lower anticoagulation levels are offered, utilizing a single value goal rather than the traditional therapeutic range. Perioperative management of anticoagulation is discussed in light of the available literature, and major drug interactions are reviewed.