Platelet-rich plasma (PRP) is postulated to decrease postoperative mediastinal chest tube drainage (MCTD) and allogeneic blood transfusions (ABT) after surgery with cardiopulmonary bypass. However, recent metaanalysis of the literature reveals that few good quality (therapeutic yield) trials that show a benefit have been published. The potential hemodynamic instability caused by plateletpheresis has not been emphasized. We studied the effect of plateletpheresis on MCTD, ABT, and hemodynamic stability in reoperative coronary artery bypass graft patients, a group perceived to be at high risk for ABT. Ninety patients were randomly assigned to Pheresis or Control groups. epsilon-Aminocaproic acid was given to all patients. Hemodynamic instability was assessed by degree of volume and inotrope resuscitation required. Part of the sequestered platelet volume was used to make autologous platelet gel, which was applied as a wound sealant. Mean pheresis yield was 30% +/- 7% of the circulating platelet mass or 6.4 +/- 2.2 allogeneic platelet unit equivalents. Total MCTD did not differ between the groups. There were no differences in mean packed red blood cell, platelet, and plasma transfusion rates. Overall, 52% of the Pheresis group received ABT, versus 55% of the Control group. Fifty-three percent of the Pheresis group patients exhibited significant hemodynamic instability, versus 27% of the Control group (P < 0.05). This study was unable to show any reduction in MCTD or ABT, although the plateletpheresis technique may offset platelet dysfunction caused by aspirin or increased blood exposure to nonbiologic surfaces, or it may compensate for lack of antifibrinolytic use. The significantly increased incidence of hemodynamic instability in the Pheresis group means that the risk/benefit ratio must be determined for individual cardiac surgical units.