Preoperative platelet-rich plasmapheresis has been suggested as a means of reducing homologous blood transfusions in cardiac surgical patients. The current study evaluated this technique in patients undergoing repeat cardiac operations. Fifty-two patients undergoing repeat myocardial revascularization and/or valve replacement were evaluated in a prospective randomized controlled study design. Autologous platelet-rich plasma (PRP) was harvested after the induction of anesthesia in the experimental group. After reversal of heparin, each patient received his or her autologous plasma. Patients in the control group did not have plasmapheresis and received standard transfusion therapy if coagulation variables were abnormal and a coagulopathy was clinically evident. Routine coagulation tests, thromboelastography (TEG), perioperative bleeding, and transfusion requirements were compared in the two groups. Forty-four patients completed the study. A significantly larger volume of packed red blood cells (PRBCs) was transfused in the PRP group than in the control group (P = 0.03). Platelet and fresh frozen plasma (FFP) transfusions did not differ between the two groups. Mediastinal tube drainage did not differ between the two groups. During PRP infusion, 60% of the patients required treatment for moderate hypotension (mean arterial pressure [MAP] < 60 mm Hg). Only 16% of control patients required treatment for hypotension during the comparable time period (P < 0.05). No patient who completed the study returned to the operating room for postoperative bleeding. These data suggest that PRP did not reduce postbypass bleeding or transfusion requirements in repeat cardiac surgical patients. Moreover, the incidence of hypotension during PRP reinfusion introduces a potential risk to the procedure in the absence of any obvious benefit.