This case report describes the prolonged general anesthetic management of a 41-year-old woman with antiphospholipid syndrome (APS), systemic lupus erythematosus, and previously undiagnosed decreased cardiac function who underwent planned partial resection of the left tongue, tracheostomy, neck dissection, and pedicled flap reconstruction. This was immediately followed by emergent surgery to salvage the flap, and 1 month later, revision of the soft tissue flap was performed. A preoperative echocardiogram was performed because of her various risk factors, which identified lateral wall hypokinesis and reduced left ventricular ejection fraction of 40%, despite no known cardiovascular disease. However, cardiology consult determined no additional treatment was needed before the surgery. Multiple antithrombotic strategies were used, including elastic stockings, intermittent pneumatic compression devises, and heparin bridging. During the general anesthetic, stroke volume variation (SVV) was used to assess cardiac function and guide fluid management. There were no signs of systemic thrombosis, although the free flap reconstruction was abandoned because of a thrombus in the vascular anastomosis. Cardiac function can deteriorate in APS patients because of coronary and/or microvascular thrombosis. Therefore, it is necessary to evaluate cardiac function, regardless of a known history of cardiovascular disease. Moreover, additional monitoring (ie, SVV) may be useful during prolonged general anesthetics for patients with APS and cardiac dysfunction.