Background: Sickle cell anemia (SCA) is a genetic disorder characterized by recurrent vaso-occlusive crises (VOC). Clinical experience with hydroxyurea (HU) for patients with sickle cell disease (SCD) has been accumulating for the past 25 years. Objectives: The present study was carried out to identify the effects of Hydroxyurea on HbF level in patients with SCD.Materials and Methods: This is a retrospective study carried out on 120 SCD patients; 60 cases were on HU treatment (group A) and 60 cases were not receiving HU treatment (group B), then according to level of HbF% after HU treatment, (group A) was subdivided into group A1 groupA2 according to changes in HbF %. Details of HU therapy and laboratry data before and after it were recordedResults: HU well tolerated, 41(68.3%) had no side effect. There was significant reduction of frequency of VOC/year, frequency of blood transfusion/year and number of hospital admission/year. There were significant increases in Hb F, total Hb, and MCV over time. Hu was effective in group A1 and A2 in spite of the difference in effect on HbF.Conclusion: hydroxyurea reduces the clinical complications SCD patients. It is safe and well tolerated. Hemoglobin F level does not affect the severity of disease and the improvement of clinical manifestation of most Patients with low HbF levels may be explained by that Hydroxyurea can work by other mechanism rather than raise HbF level.