During recent years, piggyback liver transplantation (pOLT) with preservation of the retrohepatic vena cava has been introduced in adults. The objective of this study was to evaluate hemostatic changes associated with this transplantation technique. Fifty-seven patients undergoing elective pOLT for endstage liver disease were studied. Most significant changes were observed after graft reperfusion, when PT showed a 49% decrease and activated partial thromboplastin time (aPTT) as well as TT a 2- to 3-fold prolongation. At the same time, factors of the extrinsic coagulation pathway (II, V, VII) revealed an overall 50% decline. Similar changes were observed for antithrombin III (ATIII) and fibrinogen plasma levels. However, only 42% of all patients required intraoperative substitution with coagulation components. There was an association between preoperative fibrinogen (<1.7 g/dl) and ATIII (<50%) plasma levels and the substitution requirement. Multiple linear regression showed a significant correlation between preoperative ATIII activity and intraoperative blood loss. Despite a marked impairment of hemostasis, pOLT can frequently be performed with minimized substitution therapy.