Purpose: To give a better understanding of primary AE, the clinical characteristics and the possible therapeutic approaches. Background: Angioedema (AE) is a non-pitting, non-itching swelling of skin or mucosa. The symptom can become life-threatening if located in the airways. Primary (monosympto-matic) AE is a manifestation of several different diseases and the diagnosis is not always straight-forward. The aetiological and pathophysiological factors of primary AE are not completely clarified. There is a need for further investigation. Patients and Methods: This was a retrospective cohort study of patients referred to an outpatient dermatology clinic in a tertiary care hospital for clinical assessment due to primary AE in the period from 1996 to 2014. Results: A total of 315 patients were identified with primary AE. The most frequent subtype was idiopathic AE (42.5%) and the second most common was angiotensin-converting enzymeinhibitor (ACEi)-induced AE (31.1%). Three patients were diagnosed with hereditary AE and one patient was diagnosed with acquired C1-inhibitor deficiency. At least 107 (34.0%) patients had established histaminergic AE. More than 1/3 of the patients were treated in an emergency room or hospitalized due to AE. A 98.1% of patients had experienced AE in the head and neck area. Seven patients were in the need of acute airway intervention. Six of these had ACEi-induced AE. Female sex and smoking were found to be risk factors for developing AE. Conclusion: The most frequent diagnoses were histaminergic-, non-histaminergic idiopathic AE and ACEi-induced AE, whereas complement C1-inhibitor deficiency was rare. Histaminergic AE made up a substantial group of patients with primary AE. Even though there are different pathophysiological causes of AE, many cases have overlapping clinical manifestations, which make diagnosis and treatment difficult.