A subset of patients with angioedema (AE) and urticaria has histamine releasing autoantibodies. The histamine release test (HR-test) has been used as a tool in chronic urticaria to define the autoimmune subgroup and may possibly guide the clinician to a more personalized therapy, like omalizumab and cyclosporine. The prevalence and value of positive histamine releasing autoantibodies in monosymptomatic AE is sparsely described in the literature. The purpose of this study was to report the prevalence of positive histamine releasing autoantibodies in a cohort of patients with recurrent AE and evaluate the usefulness of this test in AE patients. We performed a retrospective cohort study of 612 patients referred due to AE between 1995 and 2013. HR-test results were available in 404 patients. In the sub-group of patients with AE and urticaria, 17.3% had a positive HR-test but only 4.3% of patients with mono-symptomatic AE had a positive HR-test. No statistically significant treatment benefits of antihistamines, corticosteroids or adrenaline were found comparing patients with angioedema +/- urticaria based on the result of the HR-test (negative / positive). Thus, the HR-test result cannot be used as predictor of the efficacy of anti-allergic treatment.