Each year there are a substantial number of emergency department (ED) visits for angioedema and allergic reactions in the United States. Angioedema is commonly mistaken for an allergic reaction, possibly affecting the treatment rendered. We sought to determine the characteristics of U.S. ED visits for acute angioedema and to determine their differences from visits for allergic reactions. We used 2001-2009 data from the National Hospital Ambulatory Medical Care Survey. Using ED diagnoses (defined by the International Classification of Diseases, 9th Revision codes), we identified visits involving angioedema (ICD-9 277.6 and 995.1) or allergic reaction (ICD-9 995.6, 995.0, 995.4, 995.3, and 708). Accounting for the weighted sampling design, we determined the annual number of angioedema and allergic reaction cases, the characteristics of the affected patients, course of care, and patient outcomes. During 2001-2009 there were 1.05 billion ED visits, including 979,342 for angioedema and 8,814,601 for allergic reactions. These figures corresponded to 108,816 (95% CI, 82,246-132,386) annual visits for angioedema and 979,400 (CI, 874,562-1,084,238) annual visits for allergic reactions. Angioedema patients spent >3 hours in the ED and 11% were admitted to the hospital. Steroids and antihistamines were the most common treatments rendered for both angioedema and allergic reaction patients. There are >100,000 annual visits for angioedema in the United States, with key differences and similarities between allergic reaction and angioedema cases. These findings underscore the large number of angioedema cases presenting to U.S. EDs and the opportunities for novel angioedema therapy use in this setting.