Fatal hemolysis after mitral valve replacement with the St. Jude bileaflet tilting prosthesis is reported in two patients. Although one underwent re-replacement of the valve, both died from multiple organ failure and acute renal failure, respectively. Scanning electron microscopy revealed microthrombi adherent to a leaflet in one and irregular leaflet surfaces in the other. Such defects are rare but are possible causes of hemolysis in patients with the St. Jude mitral valve prosthesis.