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Prosthetic valve thrombosis is the second leading cause of prosthetic valve deterioration and is being more readily diagnosed with the use of echocardiography and multidetector cardiac CT. Presentation of valve thrombosis can be acute or subacute and any change in clinical status of a patient with a prosthetic valve should raise a suspicion of prosthetic valve thrombosis. Diagnosis entails detailed clinical examination and comprehensive imaging. The choice of therapeutic options includes anticoagulation, fibrinolytic therapy, or valve replacement. Antiplatelet and anticoagulation therapy remain the mainstay of thrombosis prevention in patients with a prosthetic valve and a personalized approach is required to optimize prosthetic valve function and minimize the risk of bleeding.