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Background: Immunoglobulin E (IgE)-mediated food allergies (FAs) are increasingly common among US children and adults. Not only can living with FA impose considerable physical health impacts, but it also imposes economic burden and can negatively affect quality of life. Limited data indicate that allergy to multiple foods (multi-FA) also may be common, but much remains unknown about its distribution and determinants., Objective: To characterize the prevalence, characteristics, determinants, psychosocial burden, and distribution of multi-FA among a large, nationally representative sample of US children and adults., Methods: A US population-based survey was administered. Estimates of multi-FA prevalence, conditional frequencies of multi-FA combinations, and associated factors were derived. Latent class analyses were conducted using 9 dichotomized indicators of specific FA prevalence, which were used to determine factors associated with latent class membership and characterize FA-related psychosocial burden within each class., Results: Surveys were completed for 38,408 children and 40,443 adults. Among children and adults meeting established symptom-report criteria for FA, an estimated 40% and 48% had multi-FA, respectively. Among pediatric and adult populations with convincing FAs, the lifetime reported prevalence of physician-diagnosed atopic comorbidities increased significantly as the number of reported current convincing FAs increased, as did the proportion reporting multi-FA-related health care utilization and higher perceived psychosocial burden. Latent class analyses suggested the existence of the following 4 key latent phenotypes of multi-FA: milk and egg-dominant, seafood-dominant, peanut and tree nut-dominant, and broadly multi-food allergic., Conclusion: The US population-level burden of multi-FA is high among both children and adults, and data indicate the presence of 4 major phenotypes of multi-FA in both populations., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)