The aim of this study was to determine the effect of human milk feeding during NICU hospitalization on neurodevelopment at 24 months of corrected age in very low birth weight infants. A cohort of 316 very low birth weight newborns (weight ≤ 1500 g) was prospectively enrolled in a follow-up program on admission to the Neonatal Intensive Care Unit of S. Orsola Hospital, Bologna, Italy, from January 2005 to June 2011. Neurodevelopment was evaluated at 24 months corrected age using the Griffiths Mental Development Scale. The effect of human milk nutrition on neurodevelopment was first investigated using a multiple linear regression model, to adjust for the effects of gestational age, small for gestational age, complications at birth and during hospitalization, growth restriction at discharge and socio-economic status. Path analysis was then used to refine the multiple regression model, taking into account the relationships among predictors and their temporal sequence. Human milk feeding during NICU hospitalization and higher socio-economic status were associated with better neurodevelopment at 24 months in both models. In the path analysis model intraventricular hemorrhage-periventricular leukomalacia and growth restriction at discharge proved to be directly and independently associated with poorer neurodevelopment. Gestational age and growth restriction at birth had indirect significant effects on neurodevelopment, which were mediated by complications that occurred at birth and during hospitalization, growth restriction at discharge and type of feeding. In conclusion, our findings suggest that mother's human milk feeding during hospitalization can be encouraged because it may improve neurodevelopment at 24 months corrected age.