Objective: To systematically review observational studies reporting long-term neurodevelopmental outcomes in very low-birth-weight neonates surviving after necrotizing enterocolitis (NEC).Data Sources: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health), and proceedings of the Pediatric Academic Societies (published in Pediatric Research since 1970) were searched in June and September 2006. The reference lists of identified studies and personal files were searched.Study Selection: All studies with a control group were eligible for inclusion.Main Outcome Exposure: Necrotizing enterocolitis (stage II or higher) vs no NEC.Main Outcome Measure: Neurodevelopmental impairment at 1 year or older of corrected age.Results: Eleven nonrandomized studies, including 5 with "matched controls," were included in the analyses. The risk of long-term neurodevelopmental impairment was significantly higher in the presence of at least stage II NEC vs no NEC (odds ratio, 1.82; 95% confidence interval, 1.46-2.27). Significant heterogeneity (I-2=47.9%; P = .06) between the studies indicated variations in patient, illness, and intervention characteristics and in follow-up methods. Patients with NEC requiring surgery were at higher risk for neurodevelopmental impairment vs those managed medically (odds ratio, 1.99; 95% confidence interval, 1.26-3.14). Results of analyses based on study design, follow-up rate, and year of birth were not statistically significantly different from those of the overall analysis. Risk of cerebral palsy and cognitive and severe visual impairment was significantly higher in neonates with NEC.Conclusion: Survivors of stage II or higher NEC are at risk for long-term neurodevelopmental impairment, especially, if they require surgery for the illness.