Hereditary angioedema (HAE) is a rare inherited disorder of complement factor C1 inhibitor. HAE is frequently confused with angioedema (AE), and little is known about emergency department (ED) or hospital utilization by patients with attacks in the United States. We examined hospitalizations and ED utilization for HAE and AE in two large nationally representative databases. We evaluated annual rate and resource use of HAE (International Classification of Diseases, Version 9, Clinical Modification [ICD-9-CM] code 277.6) and AE (ICD-9-CM code 995.1) hospitalizations within Nationwide Inpatient Sample (NIS), part of the Agency of Healthcare Research and Quality’s Healthcare Costs and Utilization Project (AHRQ-HCUP), for 2007. We also used AHRQ-HCUP’s 2007 Nationwide Emergency Department Sample (NEDS) to study annual rates of ED visits and subsequent hospitalizations with these conditions. There were 1691 hospitalizations with HAE and 22,572 with AE (4.25 HAE and 57.08 AE cases/100,000 hospitalizations). HAE was the principal diagnosis (PD) in 46.0% and AE in 62.5%. In aggregate, HAE and AE PD hospitalizations accrued 35,000 hospital days and hospital costs of $63 million. There were 2282 ED visits with HAE and 112,105 ED visits with AE (1.87 HAE and 91.64 AE cases/100,000 ED visits). HAE occurred as a PD in 51.2% and AE occurred as a PD in 80.0%. Forty-five percent of HAE patients and 18.3% of AE patients required hospitalization. HAE and AE ED use and hospitalization burden are substantial. Because diagnostic uncertainty is likely, HAE-related proportion of patients and resource use are probably underestimated. Clinical validation of current case definition would be useful, because administrative data may present an attractive source for investigating these populations.