OBJECTIVE To validate King's College Hospital criteria (KCHC) in children with non-acetaminophen induced pediatric acute liver failure (PALF) and to determine whether re-optimizing the KCHC would improve predictive accuracy. METHODS We used the PALF study group database. Primary outcomes were survival without liver transplantation vs death at 21 days following enrollment. Classification and regression tree analysis was used to determine if modification of KCHC parameters would improve classification of death vs survival. RESULTS Among 163 patients who met KCHC, 54 patients (33.1%) died within 21 days. Sensitivity of KCHC in this cohort was significantly lower than in the original study (61% vs 91%, P = .002), and specificity did not differ significantly. The positive predictive value (PPV) and negative predictive value (NPV) of KCHC for this cohort was 33% and 88% respectively. Classification and regression tree analysis yielded the following optimized parameters to predict death: grade 2-4 encephalopathy, international normalized ratio >4.02, and total bilirubin >2.02 mg/dL. These parameters did not improve PPV, but NPV was significantly better (88% vs 92%, P < .0001). CONCLUSIONS KCHC does not reliably predict death in PALF. With a PPV of 33%, twice as many participants who met KCHC recovered spontaneously than died, indicating that using KCHC may cause over utilization of liver transplantation. Re-optimized cutpoints for KCHC parameters improved NPV, but not PPV. Parameters beyond the KCHC should be evaluated to create a predictive model for PALF.