OBJECTIVE To determine whether D-dimer fragments predictably increase during cardiopulmonary bypass (CPB), and if so, whether increases correlate with postoperative blood loss or predict postoperative coagulopathy. METHODS Prospective observational study of 65 consecutive patients undergoing first-time coronary artery bypass graft (CABG) or first-time valve replacement. METHODS Single center University teaching hospital. METHODS Male and female patients between the ages of 30 and 90 years undergoing first-time CABG or valve replacement surgery using CPB. Patients were excluded from study for prolonged preoperative bleeding time, preoperative warfarin therapy, perioperative intra-aortic balloon pump support, thrombolytic therapy in the week preceding operation, reoperation, and emergency operation. METHODS None. RESULTS Blood sampling for platelet count, prothrombin time, partial thromboplastin time, thrombin time, fibrinogen, activated coagulation time (ACT) and D-dimer concentrations was obtained at four times during each case; (1) preoperatively, after insertion of the internal jugular introducer, before insertion of pulmonary artery catheter; (2) during CPB at 28 degrees C, immediately before rewarming; (3) after heparin neutralization (20 minutes after initial protamine dose); (4) 12 to 24 hours postoperatively. Blood loss in the intensive care unit was calculated by measuring total mediastinal drainage output at 1 and 4 hours after arrival from the operating room. An initial decrease in fibrinogen was noted during bypass, but no increase in D-dimer was identified. A few patients developed a modest increase in D-dimer after heparin neutralization, but none greater than 2.0 ug/mL. Postoperatively, fibrinogen concentration increased toward baseline levels. However, this is when six patients developed significant (> 2.0 ug/mL) D-dimer formation. Results suggest appropriate physiologic response-normalization of fibrinogen with new synthesis and remodeling of clot in the operative site causing D-dimer formation. Patients with highest D-dimer levels at 12 to 24 hours postoperatively had the highest blood loss at 4 hours postoperatively, suggesting that early postoperative excess bleeding predisposed to increased clot formation and subsequent clot remodeling causing elevated D-dimer concentrations. CONCLUSIONS D-dimer concentration is not usually elevated in patients undergoing CPB when adequately anticoagulated as monitored using the ACT. When mild elevation of D-dimer occurs, it is most often after heparin neutralization and/or in the postoperative period and is not predictive of increased postoperative blood loss. Elevations of D-dimer concentrations in the postoperative period without corresponding decreases in fibrinogen concentrations may occur and do not signify coagulopathy.