BACKGROUND AND PURPOSE Sickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population. Transcranial Doppler (TCD) ultrasound is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We aimed to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes. METHODS Children with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) were prospectively recruited from pediatric outpatient clinic over a period of 9 months. We performed TCD in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA). RESULTS Of 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10±4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (P<0.001). The right MCA TAMM (Time Averaged Maximum Mean) was significantly higher than in controls (125+5.52 cm/s vs. 92.5+1.63 cm/s, P<0.001). Left MCA did not show differences. The TICA TAMM was also different between cases and controls (P<0.05). CONCLUSIONS Among Iranian children with asymptomatic SCD and without receiving recent transfusion TCD velocities are higher as compared to healthy controls but appear much lower than those observed in STOP (Stroke Prevention Trial in Sickle Cell Anemia) studies. We hypothesize that some children at high risk may be present with velocities lower than 170-200 cm/s thresholds. A prospective validation of ethnicity-specific prognostic criteria is warranted.