The antiphospholipid syndrome (APS) is a complex autoimmune disease that causes a state of hypercoagulability that can result in recurrent venous and arterial thromboses. APS may lead to cardiac manifestations requiring cardiac surgery with cardiopulmonary bypass (CPB). Perioperative anticoagulation management in APS patients is complex. This complexity arises from both the prothrombotic nature of APS and the interference of antiphospholipid antibodies (aPLs) with phospholipid-dependent coagulation assays like activated clotting time. Given that current literature on CPB management in APS patients is largely limited to isolated case reports and lacks a comprehensive synthesis, this review summarizes the cardiac manifestations of APS, challenges posed by CPB, and current strategies for intraoperative anticoagulation management, including heparin dosing, anticoagulation monitoring methods, and protamine reversal practices. We further highlight gaps in evidence and propose a practical three-category framework for managing aPL-positive patients undergoing CPB.