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Sickle cell disease (SCD) is an inherited blood disorder that leads to a variety of complications, including stroke. The use of hydroxyurea (HU) is reported to lessen the frequency and burden of stroke in SCD patients. However, less is known about the prevalence of stroke in SCD patients pre- and during the use of HU in sub-Saharan African (SSA) countries. Therefore, the study assessed stroke prevalence before and during uses of hydroxyurea among SCD patients in Tanzania. A hospital-based descriptive cross-sectional study was conducted at the sickle cell clinics in Dar es Salaam, Tanzania, from April 2023 to May 2023. A total of 228 participants were recruited, and data on demographic and clinical characteristics, HU use, and history of stroke were collected using a checklist from the respective patients’ medical records and verbal communication with the patients or caregivers. Data analysis was done using SPSS software version 25, and findings are summarized using frequency and percentages. Out of 228 enrolled SCD patients, 124 (54.4%) were females, 109 (47.8%) were aged between 6 and 12 years, 226 (99.1%) were not married, 181 (79.4%) had primary education, and 209 (95%) were unemployed. The prevalence of stroke pre-HU use was 28 (12.3%) and 6 (2.6%) after starting using HU. Out of 6 with stroke after starting using HU, 3 (50%) had a history of stroke pre-HU uses. The study showed that the prevalence of stroke among SCD patients is significantly reduced after HU use. The findings suggest the need for stakeholders to implement measures to ensure eligible SCD patients are kept on HU.