The 2014 National Heart, Lung, and Blood Institute guidelines recommend hydroxyurea for patients with sickle cell disease SS/ Sb 0 (SCD) aged ≥ 9 months. The relationship between early hydroxyurea and cerebrovascular disease (CVD) is unclear. In this single-center retrospective study of 530 patients with SCD, hydroxyurea prescriptions rose post-guideline, with lower age at initiation. CVD was lower post-guideline (2.2/100py) versus pre-guideline (4.4/100py). However, MRI screening decreased post-guideline, leading to lower CVD detection. Results suggest decreased CVD, including silent cerebral infarcts, in the era of early hydroxyurea; further analyses are needed to confirm earlier hydroxyurea initiation improves protective against CVD.