Objective: To standardize the definition of postoperative liver failure (PLF) for prediction of early mortality after hepatectomy. Summary Background Data: The definition of PLF is not standardized, making the comparison of innovations in surgical techniques and the timely use of specific therapeutic interventions complex. Methods: Between 1998 and 2002, 775 elective liver resections, including 69% for malignancies and 60% major resections, were included in a prospective database. The nontumorous liver was abnormal in 43% with steatosis >30% in 14%, noncirrhotic fibrosis in 43%, and cirrhosis in 12%. The impact of prothrombin time (PT) <50% and serum bilirubin (SB) >50 μmol/L on postoperative days (POD) 1, 3, 5, and 7 was analyzed. Results: The lowest PT level was observed on postoperative day (POD) 1, while the peak of SB was observed on POD 3. These 2 variables tended to return to preoperative values by POD 5. The median interval between hepatectomy and postoperative death was 15 days (range, 5-39 days). Postoperative mortality significantly increased in patients with PT <50% and SB >50 μml/L. The conjunction of PT <50% and SB >50 μmol/L on POD 5 was a strong predictive factor of mortality. In patients with significant morbidity, this "50-50 criteria" was met 3 to 8 days before clinical evidence of complications. Conclusions: The association of PT <50% and SB >50 μml/L on POD 5 (the 50-50 criteria) was a simple, early, and accurate predictor of more than 50% mortality rate after hepatectomy. This criteria could be identified early enough, before clinical evidence of complications, for specific interventions to be applied in due time. Copyright © 2005 by Lippincott Williams & Wilkins.