Background: Stroke is a serious complication of sickle cell anemia (SCA). Transcranial Doppler (TCD) is the risk screening tool for ischemic strokes. Objective: The objective of the study was to describe the clinical progression of children with SCA who presented with high risk for stroke by TCD or relevant changes by magnetic resonance angiography (MRA) and underwent the regular transfusion program (RTP) and/or hydroxyurea (HU) treatment between 2007 and 2018. Method: This was a neonatal retrospective/prospective cohort study with children born between 1999 and 2014 with the homozygotic form (HbSS) or Sβ0-thalassemia, who underwent TCD at least once. Results: Of the 718 children screened during this period, 675 had HbSS and 43 HbSβ0-thalassemia. In 54 children (7.5%), all with HbSS, a high risk TCD (n=45) or, when the TCD was inconclusive, MRA with cerebral vasculopathy (n=9) was detected. Of these, 51 started RTP and the families of three refused treatment. Of the 43 children with high-risk TCD who initiated RTP, 29 (67.4%) reverted to low risk. In 18 of them (62%), HU was started at the maximum tolerated dose (MTD) before transfusion discontinuation. None of these 29 patients had a stroke. Eight children (18.6%) maintained a high-risk TCD even using RTP/HU, and two had a stroke. Conclusions: TCD was confirmed as a viable tool for tracking patients with a risk for stroke. The RTP was effective in preventing the primary event. New strategies are necessary to prevent stroke using HU and new drugs, besides bone marrow transplantation.