Von Willebrand factor (vWF) is a major platelet adhesion molecule at sites of vascular injury, such as observed in ischemia/reperfusion injury following orthotopic liver transplantation (OLT). Thirty-three OLT patients were divided into groups with elevated or low markers of hepatocellular damage (high and low-HD). Whole-blood aggregometry was performed to evaluate platelet function. Multimeric analysis was utilized to evaluate functional vWF levels in the course of OLT. Donor and recipient demographics were comparable among groups. Low-HD patients demonstrated better preserved coagulation parameters on POD 1-6 if contrasted to high-HD patients. One year graft survival for the high-HD group was lower than low-HD patients (P = 0.037). Preoperative vWF-dependent platelet aggregation and functional vWF plasma levels correlated directly with alanine transaminase levels early after OLT as did the decrease of functional vWF to reperfusion. In summary, these data suggest that vWF may serve as a significant mediator of platelet recruitment and hepatocellular injury in the graft following reperfusion.