A 71-year-old woman was diagnosed with antiphospholipid antibody syndrome following an acute myocardial infarction and had been taking anticoagulants ever since. Three years later, she was hospitalized with high fever and substantial fatigue. She was diagnosed with infective endocarditis because the blood culture was positive, and scattered cerebral infarction was seen on magnetic resonance imaging, along with an iliopsoas muscle abscess and purulent discitis. She was treated with antibiotics, and her blood culture became negative; however, she was referred to our hospital for surgical treatment because of severe mitral regurgitation due to the progressive valve destruction. She also had aortic regurgitation and underwent mitral and aortic valve replacement. The mitral valve exhibited strong thickening of both leaflets, including the subvalvular tissue, and perforation was observed in the posterior leaflet, P2. The operation time was 4 h and 2 min, and the aortic clamp time was 92 min. The culture of the mitral valve leaflet was negative. She had antiphospholipid antibody syndrome and intraoperative activated clotting time (ACT) management was difficult; therefore, her heparin blood levels were measured and managed using HMS PLUS. The target heparin blood concentration during cardiopulmonary bypass was set at 3 mg/kg and controlled; no thrombotic tendency or increase in circuit pressure was observed during the operation, and the procedure was completed without any problem. She resumed heparin administration 6 h after the operation and continued oral anticoagulant therapy. She recovered without problems and was discharged 12 days after the operation. Management using HMS PLUS may be useful in patients with antiphospholipid syndrome undergoing cardiovascular surgery.