In the USA, asthma continues to be a major health burden, affecting 26 million Americans in 2010. Asthma exacerbations contribute to a substantial portion of the burden, accounting for 2 million emergency department (ED) visits and 330,000 hospitalizations annually. Previous studies have reported considerable sex differences in asthma prevalence and several measures of chronic and acute morbidity—for example, higher risks of hospitalization in women with asthma exacerbation. Although national surveys have reported the sex differences in asthma, there have been no recent nationwide studies that examine sex differences in hospitalization risk in ED patients. In this context, we used a nationally representative database to investigate sex differences in the risk of hospitalization in children and adults presenting to US EDs with asthma exacerbation. We analyzed data from the 2010-2012 Nationwide Emergency Department Sample (NEDS). Details of the study design, setting, measured variables, and analysis may be found in this article’s Online Repository at www.jaci-inpractice.org. Briefly, the NEDS represents all ED visits regardless of disposition and contains information on short-term outcomes for patients admitted through all nonfederal hospital-based EDs in the USA. The NEDS is the largest all-payer ED and inpatient database in the USA. In 2012, the NEDS contained 31 million records of ED visits from 950 hospitals; this provided nationally representative data on approximately 134 million ED visits. In this study, we identified all ED visits for younger children (aged 4-11 years), older children (aged 12-17 years), and adults (aged 18-54 years), who had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for asthma (493.xx) in the primary diagnosis field during 20102012. Details of the study design, setting, data collections, and analysis may be found in this article’s Online Repository at www. jaci-inpractice.org. We excluded patients with chronic obstructive pulmonary disease. To examine the association of sex (female vs male) with risk of hospitalization, we constructed 2 logistic regression models for 3 age groups separately. First, we fitted an unadjusted model that included only sex as the independent variable, with male sex as the reference. Next, we constructed multivariable logistic models adjusting for patient-level characteristics and calendar year, with the generalized estimating equations to account for potential clustering of patients within EDs. All analyses used SAS-callable SUDAAN, version 11.0 (Research Triangle Institute, Research Triangle Park, NC) to obtain proper variance estimations that accounted for the complex sampling design. The institutional review board of Massachusetts General Hospital approved this analysis. During 2010-2012, we identified a total of 966,676 ED visits for asthma exacerbation in the USA, corresponding to a weighted estimate of 4,286,701 visits. Both in younger and older children, patient characteristics were similar between girls and boys. In adults, women were more likely to have public health insurance and chronic comorbidities (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). In younger children presenting to the ED with asthma exacerbation, the hospitalization rate was higher in girls than boys (10.8% vs 10.3%; P 1⁄4 .003). By contrast, in older children, the hospitalization rate was lower in girls than boys (6.5% vs 6.9%; P 1⁄4 .04). These results did not change materially in the multivariable models. In adults, the hospitalization rate was higher in women than men (13.6% vs 10.1%; P< .001). After adjustment for patient-level characteristics and calendar year, this association was meaningfully attenuated but remained statistically significant (OR, 1.07; 95% CI, 1.02-1.11; P 1⁄4 .004; Table I). Across all age groups, private insurance status as compared with self-pay, presence of comorbidities, and metropolitan residence as compared with rural residence were associated with a higher risk of hospitalization. Among adults, older age and higher income were also associated with a higher risk of hospitalization. To our knowledge, this is the first national study to investigate sex differences in risk of hospitalization among ED patients with asthma exacerbation. During 2010-2012, we found that women had a 35% higher hospitalization rate compared with men; however, much of this difference was attributable to patient-level characteristics that were associated with both sex and hospitalization risk. For example, women had more comorbidities on average than men and were more likely to have health insurance. Interestingly, there were disparities in magnitude of sex differences compared with previous studies. 4 However, direct comparisons of these disparities in magnitude are challenging because of the difference in study design (eg, an analysis of administrative dataset vs chart review study), setting, and patient population (eg, a nationally representative ED sample vs urban, academic EDs). Notwithstanding with the differences in study design, these data collectively indicate a disproportionate burden in acute asthma morbidity among US female adults. This observed sex disparity is consistent with previous single center studies and our recent multicenter study of ED patients with asthma exacerbation. Thus, multiple studies arrived at a similar conclusion despite different study designs, settings, and