The patient with a diagnosis of heparin-induced thrombocytopenia and thrombosis who requires urgent cardiac surgery represents a formidable challenge. Among the alternatives to heparin, argatroban has gained widespread use in non-cardiac surgery patients. The object of this communication is to report our recent experience with this agent during cardiopulmonary bypass (CPB) and to review the cases previously published in order to better define indications, dosage, monitoring and limitations in cardiac surgery patients. A case of mitral valve replacement where argatroban was used for anticoagulation during CPB is described. The literature on the subject is reviewed and the relationship between argatroban dosage and activated clotting time (ACT) is studied by regression analysis. Clotting of the oxygenator requiring prompt replacement occurred after release of cross-clamp. Upon termination of the drug, ACT remained elevated beyond the expected half-life. A significative (P<0.05) relationship was disclosed between increasing dosage and ACT, while the same relationship was absent on decreasing dosage. Because of unresolved issues like the possibility of clotting in the extracorporeal circuit and prolonged anticoagulation after discontinuing the drug, at present, the use of argatroban as a substitute of heparin during CPB should be restricted to those cases where the other thrombin inhibitors are contraindicated.