A 72-year-old woman with antiphospholipid syndrome underwent aortic valve replacement. Her preoperative activated partial thromboplastin time was 61.7 seconds and activated clotting time was 219 seconds. During cardiopulmonary bypass, the Hepcon Hemostasis Management System (HMS) Plus determined the heparin dose needed to maintain whole-body heparin at 3 U/mL. After cardiopulmonary bypass, 100 mg of protamine was administered based on heparin-protamine neutralization, and the activated clotting time decreased. We applied rotational thromboelastometry (ROTEM) to diagnose residual heparin using the INTEM/HEPTEM clotting time ratio. The HMS and ROTEM are useful for heparin-protamine control in antiphospholipid syndrome.