Abstract Background: Effectiveness of hydroxyurea (HU) in SCD is well established. Unanswered questions persist about use in African children in terms of acceptability and monitoring. We determined real-life user-barriers, safety and effects of therapy among children using HU in Nigeria. Methods: We retrieved and reviewed case notes of children on hydroxyurea (10-15mg/kg/day followed by dose escalation) from January 2017 to June 2019, checked for adherence to drugs, clinics and laboratory tests; starting dose, toxicity and benefits (hematologic, clinical, parental satisfaction). A questionnaire complemented case note findings. Results 116 patients received hydroxyurea (mean dose of 18 mg/kg/ day). Improvement in general well-being was 91.25%, reduction in bone pain 83.3%, hospital admissions 71.9%, abdominal pain 62.3%, blood transfusion 56.1%. Sixteen percent voluntarily stopped HU because of cost and side effects. Sixty-seven percent of parents complained about daily drug use, frequency and cost of monitoring. Adherence to daily HU was 88.8%, doctor’s appointments 22.8%, hematology tests 17.5%, organ function 32.5%. Five patients had mild neutropenia. No significant hepatic or renal toxicity occurred. Common side effects were abdominal pain (18.4%) and headache (13.2%). Significant increase in hemoglobin, fetal hemoglobin, MCV and reduction in absolute neutrophil counts occurred. Conclusion: Hydroxyurea at 10-15mg/kg/day is safe, effective and acceptable to parents. Monitoring is challenging. Care-giver education, support services, staff training, HU clinics may improve utilization. HU protocols that reduce monitoring and yet provide good clinical and laboratory benefits are necessary. This study adds to the implementation science strategies that is needed to increase HU use in Nigeria.