For prediction of adverse outcome (AO, defined as death or limb amputation) of invasive meningococcal disease (IMD) in children, two multivariable models were derived and validated by reviewing the data in the medical records of patients with IMD, who ranged from birth to 19 years of age, at three pediatric referral hospitals between 1985 and 1990 (derivation set, n = 153, 19 AO) and between 1991 and 1994 (validation set, n = 92, 11 AO). Variables in the derivation set significantly associated with AO (p < 0.05) were entered into a logistic regression analysis. Because coagulation studies (prothrombin time, partial thromboplastin time, and serum fibrinogen concentration) were available for only 50% of patients, two analyses were performed, either excluding (model 1) or including (model 2) coagulation studies. These analyses identified an absolute neutrophil count less than 3000/mm3, poor perfusion, and a platelet count less than 150,000/mm3 (model 1), and a serum fibrinogen concentration less than 2.5 gm/L (250 mg/dl) and an absolute neutrophil count less than 3000/mm3 (model 2), as independent predictors of AO (p < 0.05). When the models were tested on the validation set, the presence of at least two of the three predictors in model 1 had a sensitivity of 82% and a specificity of 97% in predicting AO; the presence of both predictors in model 2 had a sensitivity of 89% and a specificity of 97%. These models can reliably identify patients with IMD at high risk of AO for whom consideration of novel therapies is justified.