Objective:To investigate the value of fecal calprotectin in diagnosis and predicting severity of necrotizing enterocolitis (NEC) in preterm infants. Methods: A prospective controlled study was conducted including preterm infants with stage 2 to 3 NEC, and birth weight and gestational age-matched controls. Fecal samples were obtained both at the time of NEC diagnosis and 3-5 days later from the patients, and at similar postnatal age from controls. Results: Twenty-five infants with stage 2 to 3 NEC and 25 controls were enrolled. Median fecal calprotectin concentrations were 1,282 and 365 mu g/g at diagnosis in infants with NEC and controls, respectively. Fecal calprotectin levels of infants with NEC were significantly higher than those of the control group both in the first and second samples. Although the fecal calprotectin levels gradually decreased from the time of diagnosis to the second sampling time in stage 2 NEC, in stage 3 NEC fecal calprotectin concentrations increased to a higher level. A fecal calprotectin value of 792 mu g/g was found to be 76% sensitive and 92% specific for the diagnosis of definite NEC. Conclusion: Fecal calprotectin increases in infants with NEC and serial measurements may be useful as a noninvasive prognostic marker for progression of disease.