Background: Icatibant is the only subcutaneous treatment for acute Type I and Type II hereditary angioedema with C1-esterase inhibitor deficiency (HAE-C1-INH) licensed for self-administration in Europe. Aim: To compare the economic impact of two icatibant administration strategies: health professional-administration only (strategy 1) versus including the patient self-administration option (strategy 2). Methods:Economic evaluation model based on the building of a decision tree. Both strategies are assumed to have equivalent effectiveness. The payer (Spanish National Health System) and the social perspectives were considered. All relevant cost-generating factors were taken into account. The time horizon was one year. Sources of information included scientific evidence, official data and experts' opinion. A deterministic sensitivity analysis was carried out to quantify the underlying uncertainty in the model. Results: From the social perspective, which considers both direct (health care costs) and indirect costs (productivity losses), strategy 2 would result into average savings of 121.30 per acute attack compared to strategy 1. For Spain, this would achieve in an annual savings of 551,371. The reduction in direct costs accounts for 74% of the savings and lower indirect costs account for the remaining 26%. Savings per acute attack may range from 79.50 to 169.80; accordingly, the annual savings in Spain may vary between 90,319 and 2,315,360. Conclusion: Costs related to the management of acute HAE attacks with C1 inhibitor deficiency may be substantially reduced through interventions targeting home treatment by training patients to self-administer icatibant.