Effective long-term oral anticoagulant therapy is required in patients who have received mechanical heart valves to reduce the risk of thromboembolism. Patients with mechanical heart valves are at high risk for cardioembolic stroke due to thrombus formation on the valve’s surface. Numerous factors impact the overall risk for thrombosis, including the valve position, valve design, and additional patient risk factors such as AF or prior history of thromboembolism. Based on the findings of the only prospective study to date, dabigatran should not be used for mechanical valve prophylaxis due to a risk of higher thromboembolic events and excess bleeding. Nonetheless, it is important to keep in mind that this study does not definitively prove a total lack of efficacy of dabigatran for valve prophylaxis but rather demonstrates that the dosing strategy used was ineffective. It is also possible that other TSOACs such as the factor Xa inhibitors rivaroxaban and apixaban might prove beneficial, but unfortunately no studies have been completed. Thus, for the forseeable future, warfarin remains the only viable oral anticoagulant for prophylaxis in patients with mechanical heart valves. In view of the large number of patients with valvular disease, the complexity of taking warfarin, and the potential advantages of the newer agents, additional studies are clearly justified to further determine the effectiveness of alternative agents. Due to the high potential for serious and often fatal outcomes in these patients when prophylaxis is inadequate, it is imperative that pharmacists keep abreast of emerging information and monitor patients closely for appropriate therapy.