Background: Worldwide data on epidemiology of anaphylaxis are limited, mostly due to the difficult recording of all cases. The aims of the study are to determine anaphylaxis frequence to a general E.D. before and during COVID-19 pandemic, its association with demographic and clinical characteristics. Methods: This is a retrospective study analysing clinical records from a general E.D. of Milan in two periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). The analysis regarded demographic data, comorbidities, chronic therapies, causes, severity and adrenaline use. Globally data were assessed to find predictive risk factors for a severe reaction. Results: The frequence of anaphylaxis remained stable, (120/104129 = 0.12% in 2018-2019 and 72/66720 = 0.1% in 2020-2021). No differences in the occurrence of anaphylaxis were found in sex and in the mean age. The main causes of anaphylaxis were food (2018-2019: 53% vs 2020-2021: 51%) and drugs (2018-2019: 27% vs 2020-2021: 33%). Hymenoptera stings had a low occurrence and unidentified trigger was about 15% in each period. The severity of anaphylaxis had a similar distribution in the two-year periods. Gender, cardiovascular diseases, food allergy, drug allergy and Hymenoptera venom allergy did not influence the severity. A positive correlation was found with an increase in the mean age, especially in patients aged 50 or more (p<0.001). Angiotensin II receptors blockers, β-blockers, diuretics and proton pump inhibitors were associated with increasing severity (p<0.01). Conclusion: The anaphylaxis frequency in E.D. was not affected by the COVID-19 pandemic. Food anaphylaxis remained the most important cause of admission to the E.D. in our urban area. More studies are necessary to estimate the real incidence of all anaphylactic reactions.