Background: Acute chest syndrome (ACS) is a leading cause of morbidity and mortality in sickle cell patients, and it is often challenging to establish its diagnosis.Procedure: This was a prospective observational study conducted in a pediatric emergency (PEM) department. We aimed to investigate the performance characteristics of point-of-care lung ultrasound (LUS) for diagnosing ACS in sickle cell children. LUS by trained PEM physicians was performed and interpreted as either positive or negative for consolidation. LUS results were compared to chest X-ray (CXR) and discharge diagnosis as reference standards.Results: Four PEM physicians performed the LUS studies in 79 suspected ACS cases.The median age was 8 years (range 1-17 years). Fourteen cases (18%) received a diagnosis of ACS based on CXR and 21 (26.5%) had ACS discharge diagnosis. Comparing to CXR interpretation as the reference standard, LUS had a sensitivity of 100% (95% CI: 77%-100%), specificity of 68% (95% CI: 56%-79%), positive predictive value of 40% (95% CI: 24%-56%), and negative predictive value of 100% (95% CI: 92%-100%).Overall LUS accuracy was 73.42% (95% CI: 62%-83%). Using discharge diagnosis as the endpoint for both CXR and LUS, LUS had significantly higher sensitivity (100% vs. 62%, p = .0047) and lower specificity (76% vs.100%, p = .0002). LUS also had lower positive (60% vs.100%, p < .0001) and higher negative (100% vs.77%, p = .0025) predictive values. The overall accuracy was similar for both tests (82% vs. 88%, p = .2593). Conclusion:The high negative predictive value, with narrow CIs, makes LUS an excellent ruling-out tool for ACS. INTRODUCTIONSickle cell disease (SCD) is the most common genetic hematological disorder, accounting for over 305,000 births worldwide in 2010, with