Live donor adult liver transplantation (LDALT) utilizing right-lobe grafts is now acceptable as an alternative to cadaveric orthotopic liver transplantation (OLT). However, some LDALTs fail and require urgent OLT or result in recipient death. Our aim was to determine the basis of LDALT failure. Liver specimens from 49 LDALT recipients were evaluated and the findings correlated with clinical outcome. Ten patients (20.4%) had either early (< or = 1 month) or late (> 1 month) graft failure. Eight early failures, 7 of which occurred among our first 25 cases, were due to extensive liver parenchymal necrosis as a result of hepatic artery thrombosis (n=3), portal vein thrombosis (n=1), hyperperfusion syndrome (n=1), complete graft thrombosis (n=1) with Factor V Leiden on a regimen of therapeutic heparin (n=1), sepsis and concomitant graft dysfunction with venous outflow tract injury (n=1), and venous outflow tract thrombosis and parenchymal thermal injury with sepsis (n=1). Preoperative, intraoperative, or postoperative severe vessel wall injury was evident in 6/8 early failures. Two patients had late graft failure, 1 from recurrent hepatitis C and 1 with sepsis/multisystem organ failure. There were no significant differences in graft size, rejection episodes, or operative or ischemic times between patients with and without graft failure. In conclusion, LDALT failed in 10/49 (20%) of our patients, with 8/10 occurring within 1 month post-LDALT owing to vascular/thrombotic complications experienced during the early phase of our institutional experience. Perioperative vessel wall injury appeared to be a major factor in predicting early graft loss.