Sickle cell disease (SCD) is an inherited disease which leads to production abnormal hemoglobin. Clinical presentation may include vaso–occlusive, hematological and infectious crises. One of the common complications in SCD is stroke. Prevention of the first stroke (primary prevention) is possible by assessing the risk of stroke by transcranial Doppler (TCD) ultrasound and blood transfusions to patients with elevated TCD velocities. No studies were previously carried out in Saudi Arabia about higher TCD velocities in SCD. Further, although higher HbF expression is also associated with less severity of the SCD, no studies are available about association of HbF with TCD flow velocities are hence risk of stroke in SCD. This study has been carried out to identify SCD patients at high risk of stroke based on TCD results, and to determine the association between Hb–F levels and blood velocity using TCD results. A cross–sectional study carried out on 56 pediatric SCD, TCD ultrasounds were carried out initially at diagnosis to assess the risk for stroke and repeated after every 6 months for follow–up studies. Patients with TCD velocities higher than 199 cm/sec were enrolled in monthly packed RBCs transfusions to have HbS level around 40%. Data analysis was performed by “Statistical Package for the Social Sciences (SPSS, Version 17.0)”. Results revealed that in In our patient population, male to female ratio was 1.33:1 (32 males, 24 females) and mean age was 7.5 ± 3.42 years (range: 2–14 years). Seven (12.5%) patients had TCD velocities higher than or equal to 200 cm/second, with mean age of 4.7±1.4 years and mean HbF 7.5±3.8, which were significantly different from patient group with normal flow velocities (mean age of 7.8±3.4 years; mean HbF 20±15.9). Patients with higher TCD velocities receiving blood transfusion got velocities in normal range within 6–12 months. Most importantly, normal TCD flow velocities were significantly associated with higher HbF expression and vice versa. In conclusions our results showed low prevalence of SCD patients with higher TCD velocities which were clinically manageable by 6–12 months of regular PRBCs transfusion to prevent strokes. Moreover, normal TCD flow velocities and hence lower risk of stroke was significantly associated with the higher hemoglobin F expression and vice versa.