Individuals living with sickle cell disease experience high levels of morbidity that result in frequent utilization of the emergency department. The objective of this study was to provide updated national estimates of emergency department utilization associated with sickle cell disease in the U.S. Data from the National Hospital Ambulatory Medical Care Survey for the years 1999-2020 were analyzed. Complex survey analysis was utilized to produce national estimates overall and by patient age groups. On average, approximately 222,612 emergency department visits occurred annually among individuals with sickle cell disease, a nearly 13% increase from prior estimates. The annual volume of emergency department visits steadily increased over time, and pain remains the most common patient-cited reason for visiting the emergency department. Patient-reported pain levels for individuals with sickle cell disease were high, with 64% of visits associated with severe pain and 21% associated with moderate pain. Public insurance sources continue to cover most visits, with Medicaid paying for 60% of visits and Medicare paying for 12% of visits. The average time spent in the emergency department increased from previous estimates by about an hour, rising to approximately 6 hours. The average wait time to see a provider was 53 minutes. Utilization of the emergency department by individuals living with sickle cell disease remains high, especially for pain. With more than half of patients with sickle cell disease reporting severe pain levels, emergency department staff should be prepared to assess and treat sickle cell disease-related pain following evidence-based guidelines and recommendations. The findings of this study can help improve care in this population.