The study analyzed electronic health record data of 691 patients with sickle cell disease (mean age 26.5 years, 50.7% male) from five National Guard hospitals in Saudi Arabia from 2016–2021. Emergency department (ED) visits increased sharply from 9.2 per patient in 2016 to 38.8 in 2021 (+76.3% relative increase, P < 0.001), crossing the high utilization threshold (>33) in 2021. The number of hospitalizations increased from 6.3 to 13.6 (P < 0.001). Male gender (IRR 1.52; 95% CI 1.28–1.81; P < 0.001), older age (10-year IRR 1.08–1.50; P = 0.006), and asthma (IRR 1.29; 95% CI 1.04–1.60; P = 0.02) predicted higher ED use. Opioids were prescribed in 96.5% of ED visits, mostly for one-day use (93.5%). The findings show clinical severity of disease and reflect disparities in care.