Lepirudin is an alternative anticoagulant therapy in heparin-induced thrombocytopenia (HIT) during cardiopulmonary bypass (CPB). We report a case of a female patient with HIT referred for aortocoronary bypass graft despite persistence of antibodies to platelet factor 4–heparin complexes. Anticoagulation management is described. Whole blood hirudin concentration attempted during CPB was above 4 μg ml –1. To obtain this concentration, lepirudin administration was managed as follows: 0.1 mg kg –1 h –1 lepirudin during preoperative course, 0.2 mg kg –1 bolus just before CPB and 0.2 mg kg –1 in the priming solution, complementary boluses of 5 and 10 mg during procedure (according to whole blood ecarin clotting time). Aprotinin was administered simultaneously according to Royston protocol. Anticoagulation was monitored with whole blood ecarin time performed in the operation room (patient’s whole blood was diluted one half and one third with normal whole blood; in vitro calibration curve was constructed using normal whole blood spiked with lepirudin). CPB duration was 73 min. When measured, whole blood hirudin concentration was 3.8–5.8 μg ml –1. Total lepirudin administration was 44 mg. No haemorrhagic or thrombotic events were observed during surgical procedure and postoperative course. Despite lepirudin administration is not yet clearly precise for CPB procedure, its use seems adapted and safe in subjects without renal insufficiency but requiring precise coordination for anaesthesiological, surgical and biological teams.