Left ventricular assist device (LVAD) implantation in end-stage heart failure patients is frequently associated with hemorrhagic complications requiring reoperation. The preoperative coagulopathic profile includes prolonged prothrombin time (PT), partial thromboplastin time (PTT), and bleeding time; platelet dysfunction; decreased coagulation factor activity; and increased inflammatory markers. We compare outcomes in LVAD patients treated with preoperative plasma exchange with concurrent, nonrandomized control patients. We reviewed data from 68 consecutive elective patients who received LVADs at our institution. Thirty-five received LVADs after preoperative plasma exchange (replacement of one plasma volume of fresh frozen plasma), and 33 received LVADs without plasma exchange. Groups were comparable in age, sex, body weight, New York Heart Association class, intra-aortic balloon pump insertion, cardiac index, pulmonary capillary wedge pressure, creatinine, total bilirubin, hemoglobin levels, PT, international normalized ratio, PTT, and platelet count. Early mortality was lower in the plasma exchange group (0% [0/35] vs. 18% [6/33], P = 0.026), and postoperative chest tube drainage decreased by 33% (P = not significant). Blood transfusion requirements were similar. Perioperative mortality decreased in patients treated with plasma exchange before LVAD implantation.