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Background: Acute chest syndrome (ACS) is the leading cause of death for children with sickle cell disease (SCD). Recurrent ACS has detrimental effects on pulmonary health and health care costs. Neighborhood characteristics affect the outcomes of many pediatric chronic diseases, but their role in SCD is not well studied. In this study, we investigated the effects of area-level socioeconomic deprivation and racial composition on the recurrence of ACS., Study Design: We performed a retrospective cross-sectional analysis of clinical data from a large pediatric SCD center. Patients' residential addresses were geocoded and linked to a composite area deprivation index (ADI) and percent African American population at the level of Census block groups. The association of recurrent ACS with neighborhood characteristics was evaluated using logistic regression analysis., Results: The sample included 709 children with SCD. Residence in a socioeconomically deprived neighborhood was associated with 27% less risk of recurrent ACS, and residence in a predominantly African American neighborhood was associated with 41% less risk of ACS recurrence. The racial composition explained the protective effect of living in a high-deprivation area after adjusting for sociodemographic and clinical covariates. Demographic and clinical factors associated with recurrent ACS included older age, male gender, asthma, hydroxyurea use, and chronic transfusion therapy., Conclusions: This is the first study to report a protective effect of residing in a predominantly African American community for ACS recurrence. Further prospective studies are needed to confirm the association and to understand the mechanisms of such relationship., (© 2021 Wiley Periodicals LLC.)