Background While national guidelines for the management of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) in sickle cell disease (SCD) exist, institutional algorithms are tailored to their clinical practices. This study aims to compare institutional algorithms to each-other and to national recommendations for VOC/ACS in pediatric SCD. Procedures Algorithms were collected from children’s hospitals across the United States, and compared to recommendations made by the National Heart, Lung, and Blood Institute (NHLBI) 2014 and the American Society of Hematology (ASH) 2020 regarding management of VOC/ACS in SCD. Results: Review of 37 VOC and 17 ACS algorithms from 40 children’s hospitals showed that most followed national guidelines for diagnostic evaluation of VOC/ACS. Parenteral opioids and NSAIDs were recommended by all VOC algorithms with variations in dosing and administration. Intranasal fentanyl was recommended by 31 algorithms, with individualized pain protocol and non-pharmacological measures mentioned in 19 each. Incentive spirometry was included in 16 of 17 ACS algorithms, but only 11 of 37 VOC algorithms. Antibiotics were recommended by all ACS algorithms, but 4 used regimens different from the NHLBI recommendation. Most ACS algorithms had recommendations regarding transfusion, but with considerable variability. Intravenous fluid management strategies were also highly variable and hypotonic fluids were recommended in 6 VOC and 4 ACS algorithms. Conclusion: Internal algorithms for pediatric SCD show great variability compared to each other and with national guidelines, likely due to the lack of robust evidence supporting specific recommendations. Prospective studies are crucial to fill these evidence gaps with the overall goal to improve patient care.