OBJECTIVES: Icatibant, a specific bradykinin-B2 receptor antagonist, is approved for symptomatic treatment of acute attacks of HAE in adults with C1-esterase-inhibitor deficiency. Although no treatment-related serious adverse events were reported during randomized clinical trials with icatibant in HAE, a study of outcomes in normal clinical practice is important since bradykinin-B2 receptor antagonism is a new therapeutic approach. The Icatibant Outcome Survey (IOS) is an international, multicentre, prospective observational study designed to provide further information on the safety and effectiveness of icatibant in an unselected patient population. METHODS: The study population is all patients receiving icatibant outside of the blinded controlled studies. After obtaining approval from local Institutional Review Board or Ethics Committees, treating physicians are invited to enrol consenting patients and to participate in the study. A series of survey forms are used to record baseline data relating to relevant medical history and demographic information at study entry; details of previous HAE attacks, icatibant administration and outcomes; haematological, liver function and plasma lipid status; and any adverse events. Routine data entry occurs electronically via a secure link and participating physicians are encouraged to update records for each patient at 6‑monthly intervals. Any serious adverse events will be notified immediately in accordance with normal pharmacovigilance practice. Data harvested from the database will be summarised and scrutinised by an independent Steering Committee. RESULTS: Data collection commenced in July 2009 and the first analysis was done early 2010. CONCLUSIONS: The Icatibant Outcome Survey will provide further prospective data on safety and outcomes of use of this novel drug for acute treatment of HAE attacks in a ‘real world’ setting.