Objective To assess the role of glutamine in the prevention of necrotiziting enterocolitis (NEC) in preterm infants. Methods Two thousand seven hundred and seventeen preterm infants hospitalized in our NICU from Oct 2007 to Mar 2010 were assigned in either receiving prophylactic use of glutamine (prevention group, n = 1389) or without glutamine supplementation(control group, n = 1328). The incidence of NEC was compared between the two groups. Results There were no significant differences in sex,gestation age, birth weight, neonatal asphyxia, pneumonia, septicemia and cerebral hemorrhage between the two groups (P ＞ 0. 05). Sixty-eight infants occurred NEC in the control group(5. 12%) ,but only 35 infants occurred NEC in the prevention group(2. 52%) (x2 = 12. 590,P ＜0. 01). Conclusion The prophylactic use of glutamine may reduce the incidence of NEC in preterm infants.