Heparin-induced thrombocytopenia (HIT) is associated with a high incidence of vein graft occlusion after cardiac surgery. When HIT is suspected during the post-operative period, current guideline recommends a direct thrombin inhibitor such as argatroban to be started immediately. The aim of this retrospective study was to evaluate the safety and efficacy of argatroban in the early period after cardiac surgery. All patients who received argatroban within 72 h after cardiac surgery from September 2005 to June 2009 from a single center were included. Patient demographics, pre-operative relevant history, intra-operative events and post-operative data were collected and analyzed. The primary endpoints were bleeding, thrombotic complication during or after argatroban administration, and in-hospital mortality. The study population comprised 31 patients administered argatroban within 72 h after cardiac surgery. Argatroban was started a mean of 1.7 days after surgery (median dose, 0.66 μg/kg/min; median duration, 5.9 days). Twenty patients (64.5%) experienced bleeding; episode driven entirely by the need for blood transfusion. No new thromboembolic complication occurred during or after argatroban infusion. One patient died from aspiration pneumonia. Compared to those without bleeding complications, patients who bled had longer operation times and increased use of intra-aortic balloon pump. However, argatroban therapy including the starting time, median dose, infusion duration, and activated partial thromboplastin times showed no difference between the two groups. In cardiac surgery patients with clinical suspicion of HIT, early postoperative use of argatroban seems well-tolerated and associated with a low risk of thrombotic events.