The role of true cold ischemia times (CIT) and rewarming ischemia times (WIT) in determining outcome after liver transplantation was investigated in 230 adult recipients. Using multivariate analysis, WIT (time from the start of implantation until restoration of arterial and portal blood supply) and donor intensive care stay (P = 0.04 and 0.0004, respectively) but not CIT (the time from donor portal vein flushing until the graft was removed from University of Wisconsin solution; P > 0.30) emerged as independent determinants of graft survival. In the small number of patients with a WIT of greater than 180 minutes, there were reductions in graft survival (58% v 80% for WIT greater than 180 minutes) but these just failed to reach significance (P = 0.055). CIT had no influence on graft survival using cut-offs of 12 or 18 hours. A WIT of greater than 180 minutes was associated with an increased median area under the curve of day 1 through 7 serum bilirubin (1,370 v 915 μmol/L · day; P = 0.048) and trends towards an increased incidence of primary graft nonfunction or dysfunction (22.2% v 6.2% for WIT of less than 180 minutes; P = 0.065) and the day 1 through 7 area under the curve of serum aspartate aminotransferase (3,310 v 1,440 IU/L · day; P = 0.092). A prolonged CIT (greater than 18 hours) led to a prolonged hospital stay (69 v 31 days; P = 0.03), an increased area under the curve of day 8 through 14 serum bilirubin (2,500 v 995 μmol/L · day; P = 0.003), and a trend towards an increased incidence of initial poor graft function (33.3% v 6.3% for less than 18 hours; P = 0.092). The incidence of acute rejection increased (to 64.3% from 53.4%; P = 0.04) in patients with preservation injury (serum aspartate aminotransferase greater than 1,500 IU/L during the first 2 postoperative days). True CIT and WIT are important determinants of outcome after liver transplantation.