PROJECT SUMMARY Sickle cell disease (SCD) is an inherited blood disorder affecting approximately 36,000 children in the United States, approximately 90% of whom are Black. The disease is characterized by recurrent, severe pain crises which result in high rates of emergency department visits and hospitalizations, and decreased quality of life. The National Heart, Lung and Blood Institute, as well as the American Society of Hematology, have endorsed pain management guidelines regarding the timeliness of care for children presenting with these acute pain crises. These evidence based guidelines are infrequently followed, resulting in increased pain and hospitalizations. In additional to other barriers to following the guideline, structural racism has been proposed as a significant contributor and the New England Journal of Medicine recently called for the institution of SCD- specific pain management protocols to combat structural racism and reduce time to opioid administration. Our long-term goal is to improve the care and health outcomes of children with acute painful vaso-occlusive crisis treated in the emergency department. Our overall aim is to test a care pathway using multifaceted implementation strategies to increase guideline adherent care for children in the emergency department with acute painful vaso-occlusive crisis. Our primary aims are: 1) To compare the primary implementation outcomes of Reach, Adoption, and Implementation for the care pathway for treatment of children with acute painful vaso- occlusive crisis in the emergency department, between control and intervention groups and 2) To compare the primary clinical outcomes of guideline adherent care for opioid dose timing, hospitalization rates, and pain scores for the care pathway for the treatment of children with acute painful vaso-occlusive crises in the emergency department between control and intervention groups. We will test these aims using a randomized, multicenter stepped wedge design to conduct a type III hybrid effectiveness-implementation trial of the care pathway. Our proposal will institute the care pathway across seven emergency departments with the goal of improving guideline adherent care for children with SCD presenting with an acute pain crisis, thereby improving pain, decreasing hospitalizations and improving quality of life for this vulnerable population.