Hereditary angioedema (HAE) is a rare inherited disorder of complement factor C1 inhibitor. There are ∼6000 HAE cases in the United States, nearly one-half of whom suffer a monthly exacerbation. Little is known about hospital use patterns by patients with HAE attacks in the United States. This study was designed to examine burden, epidemiology, and outcomes of hospitalizations among HAE patients. We evaluated epidemiology, resource use, and discharge destinations of HAE (ICD-9-CM code 277.6) hospitalizations within the NIS, part of Agency's for Healthcare Research and Quality Healthcare Costs and Utilization Project in 2004 through 2007. There were 10,125 hospitalizations with HAE, of which 3216 (31.8%) had HAE as the principal diagnosis (HAE-PD). Two-thirds of all HAE hospitalizations were among women, and 60% were white. Hypertension was the most common comorbidity (26.9%, all HAE, and 28.0%, HAE-PD). Mortality was 1.4% in HAE and 0.3% in the HAE-PD group. Mean hospital length of stay (3.7, 95% CI 3.0-4.4 days vs. 5.0, 95% CI 4.6-5.4 days) and costs ($4,760, 95% CI $3,612-$5,907 vs. $8,383, 95% CI $7,432-$9,334) were lower in HAE-PD than in the HAE cohort. Although >80% in each group were discharged home routinely, 15.9% of HAE and 4.9% of HAE-PD required either home health care or a transfer to another short-term hospital or a skilled nursing facility. HAE hospitalization volume is substantial. Because diagnostic uncertainty is likely, HAE and its related resource use may be underestimated. HAE prevention strategies need to be examined in the context of these outcomes.