Introduction: In addition to preventive measures (wearing masks, hand hygiene, isolation), mass vaccination of the population remains the most effective means of combatting the COVID -19 pandemic. One of the serious hypersensitivity reactions to the vaccine is anaphylaxis. The aim of this study was to present the experience of the Clinical Hospital Center (CHC) Rijeka with screening and vaccination of patients at increased risk for anaphylaxis or similar severe allergic reaction to the SARS-CoV-2 vaccine. Participants and Methods: The study included data from all patients registered in the electronic consultation system of CHC Rijeka in 2021, in whom vaccination in hospital setting was indicated and who had received at least one dose of the vaccine against COVID -19 in the same year. The inquiry about the need for vaccination at the day hospital was made by a general practitioner, and the indication was made by a team of hospital allergologists. Only Pfizer’s vaccine (Comirnaty®) was used for vaccination. Results: In 2021, a total of 451 patients were vaccinated based on the prior e-consultation. Of these, 138 received only the first dose of the vaccine, 308 received both doses, and five patients received three doses. The most common indication for in-hospital vaccination was a history of anaphylaxis or anaphylactoid reaction, in 330 (73.2%) patients. A total of 97 patients (21.5%) were referred for a history of non-anaphylactic allergic reaction, 17 (3.8%) for angioedema, and seven patients (1.6%) for other reasons. None of the patients vaccinated at the day hospital developed an anaphylactic reaction to the SARS-CoV-2 vaccine. A total of six patients reported mild reactions after vaccine administration. Conclusion: In the context of COVID -19 morbidity and mortality, the benefit of vaccination far outweighs the risk of anaphylaxis, which is readily treatable in the hospital setting. However, caution and prolonged monitoring is still warranted when vaccinating individuals with a history of anaphylaxis or allergy to any of the components of the administered vaccine.