Objective: to identify lung ultrasound (LUS) findings associated to acute chest syndrome (ACS) and establish a LUS risk score for the development of ACS in children with sickle cell disease (SCD). Methods: a prospective observational study including children with SCD and signs and/or symptoms of lower airway infection were evaluated by LUS and chest radiography (CXR) at admission and 48 hours later (follow-up) and observed regarding the development of ACS during hospitalization. Results: 110 children were evaluated, of whom 66 (60%) developed ACS. At admission, LUS score greater than one showed sensitivity, specificity, and accuracy of 77.3%, 84.1% and 80.0% versus 53.0%, 100% and 71.8% on CXR. ACS diagnosis was unlikely for a LUS score of zero, likely for a score of one or two and very likely for a score greater than two. Regarding follow-up exams, LUS score greater than one showed sensitivity, specificity, and accuracy of 98.5%, 72.0% and 91.2% versus 90.2%, 100% and 92.3% on CXR. ACS diagnosis was very unlikely for a LUS score of zero, likely for a score of one and very likely for a score greater than one. Conclusion: LUS is an effective tool for the diagnosis of ACS with superior sensitivity and similar accuracy compared to CXR. The LUS score was able to assess risk for development of ACS in children with SCD and clinical suspicion of ACS.