Without intervention, 11 percent of children with sickle cell anemia will sustain a stroke before the age of 20. The STOP 2 follows on the recently completed NHLBI trial, Stroke Prevention Trial in Sickle Cell Anemia (STOP 1), which found that patients at high risk for stroke could be identified using transcranial Doppler (TCD) ultrasound, and that the incidence of stroke could be reduced by 90 percent in those children by periodic blood transfusion for at least 36 months. However, chronic intermittent blood transfusions are cumbersome, expensive and associated with morbidity from iron overload. Thus, this study to determine if transfusion can be safely halted after 30 months of treatment is critically important to the continued clinical care of patients with sickle cell disease at risk for stroke.