Due to similarities between the pathophysiological mechanisms of hereditary angioedema (HAE) and COVID-19, it has been hypothesized that SARS-CoV-2 infection may trigger HAE attacks or, alternatively, that HAE patients may experience different of COVID-19 disease severity. Furthermore, the potential for COVID-19 vaccination to trigger angioedema attacks in patients with HAE is still not completely defined. The objective is to characterize the exacerbations and clinical manifestations associated with COVID-19 infection and describe the adverse effects of COVID-19 vaccination in patients with HAE. Retrospective observational, descriptive, non-interventional, multicenter study conducted in four Allergy Units and Departments in Central Portugal between March 2020 and July 2022. HAE patient data were obtained from electronic medical records. The study included 34 patients (67.6% female): 26 with HAE type 1, 5 with HAE type 2, and 3 with HAE with normal C1 inhibitor. Most patients with HAE type 1 and 2 were receiving long-term prophylaxis. Among the 32 patients who received COVID-19 vaccination, 86 doses, were administered with one angioedema attack (1.2%) associated with vaccination. A small increase in the average number of attacks was observed in the year following COVID vaccination (7.1 6.2 in the previous year, p = 0.029), however, this difference is unlikely to be clinically significant, as the context of the COVID-19 pandemic likely introduced numerous confounders. During the study period, 16 HAE patients had COVID-19, all presenting with mild disease. Four out of 16 patients (25%) reported angioedema attacks during COVID-19, and 43.8% during the convalescence period (3 months after infection). Patients with HAE can safely receive COVID-19 vaccination. The severity of COVID-19 infection does not appear to be increased in HAE patients.