Sickle Cell Disease SCD, an autosomal-recessive disorder in which the abnormal gene product is an altered hemoglobin -chain, typically man- ifests very early in life. Signs and symptoms associated with SCD are the result of chronic anemia or acute vaso-occlusive crises, most commonly manifesting as painful episodes. Complications of SCD include acute chest syndrome, pulmo- nary hypertension, bacterial infections, and organ infarctions, especially stroke. Other effects include cognitive deficits related to MRI-demonstrated strokes and otherwise asymp- tomatic white matter hyperintensities.547,548 Stroke is a major complication of SCD, with the highest stroke rates occurring in early childhood. The prevalence of stroke by 20 years of age is at least 11%,549 with a substantial number of strokes being silent strokes on brain MRI.548 Stroke prevention is most important for patients with homozygous SCD because the majority of the SCD-associated strokes occur in these patients. TCD ultrasound identifies those at high risk of stroke, allowing evidence-based decisions about optimal primary stroke prevention.550,551 Although the exact mechanism by which high blood flow velocities increase the risk for ischemic stroke is not known, the association is well established. The risk of stroke during childhood in those with SCD is 1%/y, but patients with TCD evidence of high cere- bral blood flow velocities (time-averaged mean velocity >200 cm/s) have stroke rates >10%/y.551,552 Retrospective analysis of the Stroke Prevention Trial in Sickle Cell Anemia (STOP) data suggested that velocity >170 cm/s in the anterior cerebral artery is associated with increased stroke risk after controlling for the middle cerebral artery/internal carotid artery veloci- TCD surveillance of children with SCD remains the gold standard for stroke risk prediction, and its increased use coincides with a decrease in stroke among the pediatric SCD The optimal frequency of screening to detect patients at high risk has not been determined. 