Cardiopulmonary bypass circuits cause morbidity during cardiac operations. Plasma proteins and cellular components are stimulated by contact with the cardiopulmonary bypass circuit and can cause bleeding and postperfusion syndrome. This is especially true in patients undergoing reoperative cardiac procedures, which carries a higher risk of postoperative bleeding and prolonged ventilation compared with primary cardiac surgical procedures. Recently, cardiopulmonary bypass circuit surfaces have been coated with antithrombotic agents to improve their biocompatibility. This study evaluated the effect of a heparin-coated cardiopulmonary bypass system (Duraflo II, Baxter Bentley Healthcare Systems, Irvine, Calif.) on thrombin formation, platelet stimulation, and leukocyte activation in patients undergoing reoperative coronary artery bypass grafting or valve operation. Fifty patients were selected and randomly assigned to a standard noncoated control system (n = 26) or the Duraflo heparin-coated system (n = 24). Similar heparin doses were used in both groups (3 mg/kg). The heparin-coated group used a completely heparin-coated bypass circuit including the cardiotomy reservoir; arterial filters were heparin-coated in both groups. Samples were obtained before cardiopulmonary bypass, 30 minutes into cardiopulmonary bypass, 5 minutes after crossclamp removal, and 5 minutes after protamine administration. Thrombin formation (thrombin-antithrombin III by enzyme-linked immunosorbent assays) and platelet activation (beta-thromboglobulin by enzyme-linked immunosorbent assays; P-selectin expression by flow cytometry) were assayed. Leukocyte activation was determined by quantitative and qualitative analysis of arterial filters by scanning electron microscopy in six patients from each group. In both circuits, thrombin values increased markedly 30 minutes into cardiopulmonary bypass compared with baseline values (p < 0.001) (heparin-coated, 7 +/- 5 to 96 +/- 115 ng/ml; noncoated, 10 +/- 9 to 115 +/- 125 ng/ml). Platelet activation as measured by beta-thromboglobulin (heparin-coated, 104 +/- 100 to 284 +/- 166 IU/ml; noncoated, 81 +/- 74 to 288 +/- 277 IU/ml) and P-selectin expression (heparin-coated, 1.5% +/- 1.5% to 6.4% +/- 6.1%; noncoated, 1.4% +/- 1.1% to 6.2% +/- 4.3%) also significantly increased 30 minutes into cardiopulmonary bypass compared with baseline values (p < 0.001). Platelet activation and thrombin generation did not differ between the two circuits at any time. Granulocyte activation and platelet deposition did not differ between the two circuits when arterial filters were evaluated. Both groups had similar heparin and protamine administration, blood transfusions, postoperative alveolar-arterial oxygen gradient, time to extubation, length of intensive care unit stay, and overall morbidity and mortality. Clinical outcome and blood loss did not differ between the groups. We conclude that heparin-coated cardiopulmonary bypass circuits did not improve biochemical or clinical markers of biocompatibility in a reoperative patient population.