CONTEXT: Brain injury is the most common long-term complication of congenital heart disease requiring surgery during infancy. It is clear that the youngest patients undergoing cardiac surgery, primarily neonates and young infants, are at the greatest risk for brain injury. Developmental anomalies sustained early in life have lifelong repercussions. OBJECTIVE: We conducted a systematic review to examine longitudinal studies of cognitive and/or motor outcome after cardiac surgery during early infancy. METHODS: Electronic searches were performed in Medline, the Cumulative Index to Nursing and Allied Health Literature (Cinahl), and Embase (1998-2008). The search strategy yielded 327 articles, of which 65 were reviewed. Eight cohorts provided prospective data regarding the cognitive and/or motor outcome of infants who had undergone surgery for congenital heart disease before 6 months of age. Two authors, Ms Snookes and Dr Gunn, independently extracted data and presented results according to 3 subgroups for age of follow-up: early development (1 to <3 years); preschool age (3-5 years); and school age (>5 to 17 years). Weighted analysis was undertaken to pool the results of studies when appropriate. RESULTS: All of the identified studies reported results of the Bayley Scales of Infant Development for children younger than the age of 3. Outcome data as reported by the Bayley Scales were combined for infants assessed at 1 year of age, revealing a weighted mean Mental Development Index of 90.3 (95% confidence interval: 88.9-91.6) and Psychomotor Development Index of 78.1 (95% confidence interval: 76.4-79.7). Additional analysis was limited by a lack of data at preschool and school age. CONCLUSIONS: With this review we identified a limited number of prospective studies that systematically addressed outcome in patients at the highest risk. These studies consistently revealed cognitive and motor delay in children after cardiac surgery during early infancy. Additional investigation is required to ascertain the consequences of such impairment during later childhood and into adult life.