Hydroxyurea (HU) has proven benefit in sickle cell anemia (SCA), but HU is still underutilized. The Pediatric Sickle Cell Program of Northern Virginia prescribes HU uniformly regardless of symptoms to SCA patients age ≥ 9 months and prospectively tracks outcomes. HU is prescribed to maximum tolerated dosing (MTD) to target 30% Hgb F. Longitudinal data over 10 years from 2009-2019 were analyzed in 2-year intervals for hemoglobin (Hgb), fetal hemoglobin (Hgb F), hospitalizations, transfusions, and treat-and-release ED visits. Comparing the 2-year interval prior to uniform HU implementation (2009-2011) to the last 2-year interval analyzed after HU implementation (2017-2019), HU usage increased from 33% to 93%, average Hgb increased from 8.3±0.98 to 9.8±1.3 g/dL (p<0.0001), average Hgb F rose from 13±8.7% to 26±9.9% (p<0.0001), hospitalizations decreased from 0.71 (95% CI 0.54-0.91) to 0.2 (95% CI 0.13–0.28) admissions/person-year, sporadic transfusions decreased from 0.4 (95% CI 0.27–0.55) to 0.05 (95% CI 0.02–0.12) transfusions/person-year. Treat-and-release ED visit rates remained unchanged, varying between 0.49 (95% CI 0.36-0.64) and 0.64 (95% CI 0.48-0.83) visits/person-year. By the last 2-year interval, 72% of patients had Hgb ≥ 9g/dL, 42% had Hgb F ≥ 30%, 79% experienced no hospitalizations, and 94% received no transfusions. Prescription of HU uniformly for SCA patients to achieve high Hgb F resulted in significant improvements in laboratory and clinical outcomes within 2 years that continued to improve over the next 6 years. Rigorous HU implementation uniformly in a pediatric sickle cell program is feasible, effective, and sustainable.