A 27-year-old male with a six-year history of hypereosinophilic syndrome (HES) presented with a native mitral valve thrombus, despite therapeutic oral anticoagulation. The thrombus was removed, the mitral valve replaced, and subsequent oral anticoagulation maintained at a higher level (INR 3.5). The patient developed two recurrences of mitral valve thrombosis requiring urgent reoperations, and died shortly after the second intervention. A scanning electron microscopy analysis of the native mitral valve thrombus removed during the first cardiac surgery revealed tightly packed thin fibrin strands forming fuzzy irregular structures, with areas of an almost solid fibrin clot. The fibrin networks indicated a heightened thrombin generation, and may account for a diminished susceptibility to intrinsic fibrinolysis. In conclusion, the unfavorably altered compact structure of the fibrin-rich thrombus, which formed despite adequate anticoagulation, might in part explain the recurrent valvular thrombosis. It may also represent a novel prothrombotic mechanism that operates in HES.