AbstractBackgroundDuring the COVID‐19 pandemic focus has been on polyethylene glycol (PEG) and polysorbate as these excipients are constituents in the first vaccines and possible elicitors of allergic reactions to the vaccines. We aimed to evaluate the possibility of vaccinating patients with PEG and/or polysorbate allergy against COVID‐19.MethodsTwenty‐five patients with a history of an allergic reaction to drugs, vaccines and mouth hygiene products containing PEG or polysorbate and sensitization (skin test or in vitro test) or a positive challenge were included. We re‐evaluated 19 of 21 patients diagnosed before 2021 and four new patients by skin prick tests (SPT) and Basophil Histamine Release (BaHR) for PEGs, polysorbates and approved COVID‐19 vaccines as well as measurement of specific IgE (PEG 2000, 10,000). Patients were offered vaccination based on decision points from the primary diagnosis and re‐evaluation.ResultsMost common primary elicitors were depot‐steroids and laxatives. Most patients had experienced more than one reaction. SPT was superior to BaHR test although many SPTs became negative over time. After careful re‐evaluation three patients were successfully vaccinated with the Pfizer/BioNTech vaccine. Three were vaccinated before referral. Eleven were offered the Johnson‐Johnson vaccine; four were vaccinated successfully, seven abstained. Six patients could not be vaccinated with PEG or polysorbate containing vaccines.ConclusionHypersensitivity to excipients in COVID‐19 vaccines constitutes a risk to patients with allergy to PEG or polysorbates. After diagnostic evaluation, a safe COVID‐19 vaccine could be offered to most patients, the remainders will await new vaccines containing different excipients.