The Stroke Prevention Trial in Sickle Cell Anemia (STOP) was a randomized trial to evaluate whether chronic transfusion could prevent initial stroke in children with sickle-cell anemia at high risk as determined by transcranial Doppler (TCD). The trial demonstrated a large benefit of transfusion and was halted early. After termination of the trial, patients participated in a post-trial follow-up study. More patients in the transfusion group (70%) elected transfusion for primary stroke prevention compared with those on standard care (45%). Six patients with persistently abnormal TCD results developed stroke. A minority with initially abnormal TCD results remained stroke-free without transfusion. Except for lower baseline and follow-up TCD velocities compared with those with stroke, no predictive features of this apparent lower-risk subgroup could be determined. TCD results at last testing in 108 patients that did not have stroke were: normal (44.4%), conditional (26.9%), abnormal (22.2%), and inadequate (6.5%). Patients on transfusion were more likely to have normal TCD results. Transfusion resulted in iron overload and alloimmunization, but no infection. The study provides new information on acceptance rates and long-term effects of transfusion. Persistent TCD elevation signals ongoing stroke risk. Reduction in TCD results over time without transfusion is observed in some patients and requires further study.