The feasibility of bivalirudin for anticoagulation during cardiac surgery has been confirmed in four multicenter clinical trials. Here, we report our single-center experience with bivalirudin anticoagulation in "on-pump" and "off-pump" cardiac surgery in a large number of patients with and without heparin antibodies. Data of patients who underwent cardiac surgery with bivalirudin anticoagulation between 06/2003 and 12/2007 at our institution were reviewed. Assessment included procedural success, blood loss, transfusion requirements, re-exploration rates and drug-related complications during the procedures. There were 141 patients treated with bivalirudin, of whom 40 had heparin antibodies. In 26 patients, "off-pump" coronary artery bypass grafting was performed and the remaining 115 patients had surgery with cardiopulmonary bypass (CPB). The procedural success rate after 7 days and after 30 days was 99.4%. The mean blood loss after "off-pump" surgery was 833 +/- 310 ml, with a transfusion rate of 30%. The mean blood loss after "on-pump" surgery was 750 +/- 494 ml, with a transfusion rate of 56%. Two patients needed re-exploration due to persistent hemorrhage. Overall transfusion rates were increased in patients with heparin antibodies. The current investigation demonstrates that, in experienced hands, bivalirudin anticoagulation can be performed with excellent procedural success and low complication rates during "on-pump" and "off-pump" cardiac surgery. Recent problems associated with the production of heparin have emphasized the urgent need for an alternative for use beyond the limited indication of heparin-induced thrombocytopenia.