Heparin resistance (HR) during cardiac operations is a common feature. Its aetiology often recognizes a decrease in circulating antithrombin III (AT III) due to a preoperative heparin treatment. Nevertheless, some papers highlighted the existence of HR in patients with normal values of AT III. This paper was designed in order to identify this subgroup of AT III-independent heparin-resistant patients. Five hundred consecutive patients scheduled for coronary revascularization with cardiopulmonary bypass were enrolled in this prospective trial. HR was identified in 104 (20.8%) patients. Thirty-six of them (7.2% of the total population) had a preoperative AT III activity > or = 100%, and were defined as AT III-independent heparin-resistant patients. This subgroup significantly differs from the AT III-dependent heparin-resistant group being affected by a less severe degree of HR and including less patients pretreated with heparin. Unlike the other heparin-resistant patients, these subjects do not respond to AT III supplementation aimed at reaching supranormal AT III activity values.