BackgroundCow's milk is a food allergen of public health importance both in the United States and globally. Its natural history and epidemiology have been most studied among infants and young children, but the public health burden it places on adults and older pediatric populations remains unclear. This study comprehensively characterizes the US population-level burden of cow's milk allergy (CMA), including its prevalence, severity, health care utilization, psychosocial impact, natural history, and other associated factors—including ability to tolerate extensively heated milk products—within a large, nationally-representative survey sample of US households. MethodsA cross-sectional survey was administered via web and telephone. Population level inference was based on data collected from participants recruited from National Opinion Research Center (NORC) at the University of Chicago's probability-based AmeriSpeak panel. Established dual-sample complex survey calibration methods were used to augment this sample with additional participants recruited through Survey Sampling International to increase the precision of the resulting estimates. In total, surveys were administered to a nationally representative sample of 51 819 US households from October 1, 2015, through September 31, 2016. Self-report responses from 40 453 adults and parent-proxy report for 38 408 children were analyzed. ResultsAnalyzing survey responses from 78 851 individuals, an estimated 4.7% (95% CI, 4.4%–4.9%) of the US population reported current CMA, whereas 1.9% (95% CI, 1.8%–2.1%) met symptom-report criteria for convincing IgE-mediated allergy. An estimated 0.9% (95% CI, 0.8%–1.0%) had CMA that met convincing symptom-report criteria and was physician diagnosed. Female and White respondents were more likely to report outgrowing CMA relative to males and those reporting other races and ethnicities. Individuals with CMA who reported tolerance to baked milk products were less likely to report severe reaction histories (33.5% vs 42.7%; p = .03), a lifetime history of food allergy-related emergency department visits (43.4% vs. 55.8%; p = .005), and treating a milk-allergic reaction with epinephrine (10.6 vs. 18.9%; p = .003). These individuals also exhibited less psychosocial burden on the validated Food Allergy Independent Measure (FAIM) than their counterparts with CMA who were allergic to baked forms of milk. ConclusionThese data indicate a discrepancy in reported rates of allergy to cow's milk among the US general population ranging from approximately 1 in 20 with reported CMA to fewer than 1 in 50 with physician-confirmed CMA. However, they suggest a substantial population-level burden of CMA, including substantial healthcare utilization, psychosocial burden and nutritional impacts—particularly among the approximately 30% of individuals with CMA who cannot tolerate baked forms of milk.