The reliability of procalcitonin as a predictor of invasive infection in infants <36 months of age with fever and nontoxic appearance was assessed in 868 patients, 15 (1.7%) of whom had invasive infection. The area under the receiver operating characteristic curve for procalcitonin was 0.87 (optimum cutoff 0.9 ng/mL, sensitivity 86.7%, specificity 90.5%), whereas for C-reactive protein it was 0.79 (optimum cutoff 91 mg/L, sensitivity 33.3%, specificity 95.9%). In infants with fever of <8 hours duration, the area under the receiver operating characteristic curve was 0.97 for procalcitonin and 0.76 for C-reactive protein. Procalcitonin was a useful biomarker to predict invasive infection in non-toxic-appearing infants with fever without apparent focus, particularly in febrile episodes of <8 hours duration.