A 45-year-old woman with antiphospholipid antibody syndrome (APS) and systemic lupus erythematosus was admitted because of severe dyspnea. She had undergone mitral valve replacement (MVR) using a Mosaic bioprosthesis for infective endocarditis 9 years previously. She developed congestive heart failure secondary to mitral bioprosthetic valve stenosis resulting from relatively early structural valve deterioration. She underwent a second MVR using a mechanical valve prosthesis. The explanted bioprosthesis showed marked pannus formation and mineralization with fibrin thrombus formation, especially on the outflow surfaces of the leaflets. After the second operation, she was discharged without APS-related thromboembolic events under meticulous anticoagulant and antiplatelet therapies.