Stroke, occurring in about 10 percent of pediatric patients with sickle cell disease, is one of the most devastating complications, with a high recurrence rate after the first episode. Several non-randomized studies have shown reduction in stroke recurrence when periodic blood transfusions are administered to maintain hemoglobin S under 30 percent. Periodic blood transfusions are associated with significant risks of iron overload and other complications and must be accompanied by parenteral iron chelation therapy. However, this has become a standard of care for prevention of recurrent stroke in SS children. Thus, a randomized trial of blood transfusion for secondary prevention would not be feasible because it would be considered unethical. Based on various studies, the recurrence rate is reduced from 46 to 67 percent to approximately 7 percent on transfusion therapy. Because most stroke patients are left with some neurological deficit, and face a lifetime of disability, primary prevention would have a significant impact on the management of patients. However, because of complications of blood transfusions, the hypothesis should be proven by a randomized clinical trial.