Aim: To determine the effect of neonatal glutamine-enriched enteral nutrition in very low birth weight (VLBW) infants on neurodevelopmental outcome at 2 years of age. Methods: Eighty-eight out of one hundred two infants participating in the initial study were eligible for the follow-up study (13 died, one exclusion due to a chromosomal abnormality). Neurodevelopmental outcome (neurologic status, vision, hearing and Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II) was evaluated at the corrected age of 2 years. To adjust for potential confounders, data were analyzed by multiple linear or logistic regression (for continuous and dichotomous variables, respectively) Results: Seventy-two out of eighty-eight (82%) infants participated in the follow-up study: 40 and 32 infants in glutamine-supplemented and control groups, respectively. The incidence of neither an MDI nor a PDI ≤ 85 was different in glutamine-supplemented and control groups (MDI ≤ 85: 27 and 19%, p = 0.17; PDI ≤ 85: 28 and 16% p = 0.16, respectively). The incidence of neurodevelopmental impairment was not different between both groups (OR: 2.16, 95% CI: 0.64-7.28). Conclusions: A positive effect of neonatal glutamine-enriched enteral nutrition in VLBW infants on neurodevelopmental outcome at 2 years of age was not found in this study. © 2008 The Author(s).