Prosthetic valve thrombosis is one of the life-threatening complications in patients with prosthetic heart valves. It is more common in mechanical prosthetic valves in the setting of inadequate or missing anticoagulation. Besides optimization of anticoagulation urgent surgery or thrombolytic therapy should be considered but both are associated with an increased risk for complications and mortality. We report a case of a patient with imaging data for mechanical prosthetic mitral valve thrombosis. Considering the individual patient’s characteristics and the published guidelines we decided to perform systemic thrombolysis with ultra-slow low-dose infusion of tissue-type plasminogen activator. The therapy was successful without any bleeding or thromboembolic complications.