A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) is a metalloproteinase that specifically cleaves the multimeric von Willebrand factor (VWF). Deficiency of ADAMTS13 increases the unusually large VWF multimers (UL-VWFM), which leads to platelet clumping and/or thrombus formation, resulting in microcirculatory disturbance. We serially determined the activity of plasma ADAMTS13, together with VWF antigen (VWF:Ag) and UL-VWFM, in association with the development of early graft dysfunction in 3 liver transplant recipients and 4 patients with major hepatectomy as controls. In case 1, ADAMTS13 activity decreased markedly from 108% to less than 3% with concomitant thrombocytopenia on posttransplantation day 7, when acute rejection occurred. Simultaneously, UL-VWFM were detected. During the second episode of rejection, VWF:Ag increased to 368% with the appearance of UL-VWFM, while ADAMTS13 activity was as low as 18%, indicating an imbalance between a large amount of UL-VWFM and low activity of ADAMTS13. Administration of fresh frozen plasma (FFP) together with treatment for acute rejection resulted in an improvement of ADAMTS13 activity and disappearance of the UL-VWFM. In case 2, ADAMTS13 activity promptly decreased to 9% with thrombocytopenia on day 1, when ischemia-reperfusion injury occurred. Subsequently, the ADAMTS13 activity increased steadily without appearance of UL-VWFM, and the patient recovered uneventfully. ADAMTS13 activity decreased to 15% immediately after transplantation in case 3 as well. In contrast, ADAMTS13 activity never decreased below 20% in 4 patients with major hepatectomy as controls. In conclusion, these results indicate that the kinetics of ADAMTS13 and UL-VWFM could be good indicators of adverse events after liver transplantation. Our findings not only suggest a novel mechanism for thrombocytopenia, but also provide a useful tool for diagnosis of graft dysfunction in the early stage after transplantation.