PURPOSE: Population-based surveillance of children aged 3-10 years from metropolitan Atlanta was used to determine if stroke-related neurological damage in children with sickle cell disease (SCD) is associated with developmental disabilities (DD). METHODS: School and medical records were reviewed annually to identify eligible children. Observed-to-expected ratios, P values, and population attributable fractions were calculated. RESULTS: Children with SCD had increased risk for DD (O/E = 3.2, P < 0.0001), particularly mental retardation (O/E = 2.7, P = 0.0005) and cerebral palsy (O/E = 10.8, P < 0.0001). This risk was confined to DD associated with stroke (O/E = 130, P < 0.0001; for DD without stroke: O/E = 1.3, P = 0.23). CONCLUSIONS: Children with SCD have increased risk for DD associated with stroke; thus, aggressive interventions are needed to prevent stroke in these children.