Children with sickle cell anemia (SCA) have poor growth and pubertal development. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a prospective trial evaluating the feasibility, safety, and benefits of hydroxyurea at maximum tolerated dose (MTD) for children with SCA in sub-Saharan Africa. Children 1-10 years old at 4 sites received open-label hydroxyurea with longitudinal follow-up. Height, weight, and pubertal (Tanner) staging were collected at enrollment and sequentially over 7 years of treatment. Biomarkers included insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), luteinizing hormone (LH), follicle stimulating hormone (FSH), and anti-Mullerian hormone (AMH). Hydroxyurea commenced at an average (mean±1SD) age of 5.9±2.4 years (range 1.6-10.2) for girls (n=296) and 5.4±2.4 years (range 1.3-10.1) for boys (n=310). Using natural history SCA-specific reference curves, the mean weight-for-age Z-score improved from 0.47±0.90 at enrollment to 0.69±1.00 on hydroxyurea treatment. Height increased from 0.26±0.90 to 0.42±1.00 on treatment, and BMI from 0.46±1.00 to 0.85±1.20. IGF-I remained low in many participants: mean IGF-I was -1.5 SD at baseline and -1.4 SD at follow-up in girls, and -2.3 at baseline and -2.2 at follow-up in boys. Pubertal onset was delayed in 25-30% of children, with gradual progress on treatment. AMH was low (<2.5th percentile) in 4% of girls, while 52% of boys had low AMH at baseline and 28% at follow-up. Long-term hydroxyurea treatment at MTD is associated with beneficial effects on growth with improved weight and height, and does not negatively impact pubertal development in children with SCA in sub-Saharan Africa.