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Abstract: Neurovascular complications, including strokes and transient ischemic attacks (TIAs), are common and cause significant morbidity in individuals with sickle cell disease (SCD). The Stroke Prevention Trial in Sickle Cell Anemia (STOP) (1998) established chronic transfusions as the standard of care for children with SCD at high risk for stroke. Using statewide data from the California Department of Health Care Access and Innovation (1991-2019), we determined the cumulative incidence (CMI) and rates of primary and recurrent strokes/TIAs in people with SCD pre- and post-STOP trial. For the 7636 patients included in our SCD cohort, the cumulative incidence of the first ischemic stroke was 2.1% by the age of 20 years and 13.5% by the age of 60 years. The CMI of the first intracranial hemorrhage (ICH) was 0.5% and 6.8% by the age of 20 and 60 years, respectively. Ischemic stroke rates increased in children (age <18 years; 234.9 vs 165.1 per 100 000 patient years [PY]; P = .012) and adults (age 31-50 years; 431.1 vs 303.2 per 100 000 PY; P = .031) in 2010 to 2019 when compared with the preceding decade. There was an increase in the rates of ICH in those aged 18 to 30 years and TIA in children <18 years from 2010 to 2019 when compared with the previous decade. Risk factors for strokes included increasing age, hypertension, and hyperlipidemia. These findings underscore the need for stroke prevention in adults with SCD, suggesting an emphasis on management of modifiable cerebrovascular risk factors that have been proven to be effective in the general population., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)