Heparin-induced thrombocytopenia (HIT) is being recognized in an increasing number of patients referred for cardiac surgery, as a result of previous exposure to heparin. We present a case of a patient with HIT scheduled for aortic valve replacement and coronary bypass graft surgery, who was managed with the direct thrombin inhibitor, argatroban for anticoagulation during cardiopulmonary bypass (CPB). The patient sustained continued bleeding in excess of the acknowledged half-life of the drug and required a substantial number of blood products to restore coagulation following CPB. Pertinent reports using argatroban for cardiac surgery with CPB are reviewed in the context of the present case report. The pharmacologic basis, cost analysis and resource utilization of heparin substitutes are discussed for the patient with HIT requiring CPB.