Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis. Management of persons with an immediate reaction suggestive of an allergy after the first dose remains to be defined. The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis. Management of persons with an immediate reaction suggestive of an allergy after the first dose remains to be defined. Method: Skin testing was performed with both mRNA-based vaccines. Upon a negative skin test, a 2-step (10 + 90%) revaccination protocol was performed. Positive skin tests were confirmed with a Basophil Activation Test (BAT). Results: 25'162 first doses of COVID-19 vaccines (80% from Pfizer BioNTech) were administered at the university hospital of Lausanne. Respectively, 3.47 and 1.99 immediate reactions per 10'000 doses were observed with the vaccine of Pfizer BioNTech and Moderna. An allergy workup was performed in 18 persons among who 11 were referred from external centers. 17/18 (94%) were females and 7/18 (39%) had criteria for anaphylaxis. 3/18 (17%), 2/3 with anaphylaxis, had positive intradermal reactivity after 20 minutes for both mRNA vaccines. BAT was positive in 2 persons and is pending in the third one. 14 patients had negative skin testing. Among those 8 received a 2-step re-vaccination protocol, 3 refused revaccination, and 3 wait for revaccination. 8/8 with negative tests tolerated the 2-step re-vaccination. One patient with suspicious skin tests but positive BAT developed again urticaria 7 minutes after the 90% dose. Conclusion: Only 22% of patients, all females, with an immediate reaction to the first vaccination were sensitized to the vaccine. A two-step re-vaccination protocol could be safely administered upon negative skin testing.