Antiphospholipid syndrome (APS) is a complex autoimmune disease often related to systemic lupus erythematosus. Although adequate anticoagulation is important for APS patients during cardiopulmonary bypass, clotting tests can be potentially misleading due to antiphospholipid antibodies. We performed cardiac surgery safely in two APS patients under anticoagulation monitoring determined using preoperative heparin titration. We performed heparin titration for activated clotting time to determine the appropriate heparin concentration during cardiac surgery. We changed the targeted heparin concentration considering each patient's thrombotic risks: 3 U/ml of heparin for a normal-risk APS patient and 5 U/ml for a high-risk APS patient with a history of antiphospholipid-antibody-associated thrombocytopenia. A higher targeted heparin concentration might be necessary for patients with high thrombotic risks.