Determining which patients are at highest risk of acute chest syndrome (ACS) is challenging for pediatric emergency department (PED) providers, resulting in more chest x-rays (CXR), increased radiation exposure, and higher healthcare costs. The objective of this study was to identify significant clinical predictors of ACS to better guide care. In this retrospective review, we included patients diagnosed with sickle cell disease (SCD), aged 2-12 years, who presented to the PED between 2016-2018. We compared patients who were febrile vs. afebrile on presentation, and those diagnosed with ACS vs. those who were not. A total of 424 patients met inclusion criteria, 25% presenting with fever. For febrile patients, 69% received a CXR on presentation vs. 42% of afebrile subjects (p=<0.0001). Overall, 10% of patients were diagnosed with ACS: 13% of febrile presentations vs. 9% of afebrile presentations. Patients diagnosed with ACS were significantly more likely to present with chest pain (p=0.003), tachypnea (p=0.001), hypoxia (p<0.0001), and a history of asthma (p=0.0085). Upon multivariable modeling the only significant predictors were chest pain (OR 3.3, CI 1.5-7.4) and hypoxia (OR 8.4, CI 4-17.9). Current guidelines recommend empiric treatment and a CXR for SCD patients presenting with fever, hypoxia, tachypnea, tachycardia or abnormal respiratory exam. Our data demonstrate that hypoxia and chest pain are significant predictors of ACS. Additionally, data indicated that CXRs were likely performed in excess in febrile patients. Further research is needed, but chest pain and hypoxia may focus the use of CXR on the appropriate patients.