Importance: Allergic history in individuals with confirmed anaphylaxis to a messenger RNA (mRNA) COVID-19 vaccine is common. However, the risk factors for allergy symptoms after receiving the vaccine are unknown.

Objective: To assess the association between self-reported history of high-risk allergy and self-reported allergic reactions after mRNA COVID-19 vaccination of health care employees.

Design, setting, and participants: This cohort study obtained demographic, medical, and vaccine administration data of employees of Mass General Brigham from the institutional electronic health record. Employees who received at least 1 dose of an mRNA COVID-19 vaccine between December 14, 2020, and February 1, 2021, and who completed at least 1 postvaccination symptom survey in the 3 days after vaccination were included.

Exposures: Self-reported history of high-risk allergy, defined as a previous severe allergic reaction to a vaccine, an injectable medication, or other allergen.

Main outcomes and measures: The primary outcome was 1 or more self-reported allergic reactions in the first 3 days after dose 1 or dose 2 of an mRNA COVID-19 vaccine. Multivariable log binomial regression was used to assess the association between allergic reactions and high-risk allergy status.

Results: A total of 52 998 health care employees (mean [SD] age, 42 [14] years; 38 167 women [72.0%]) were included in the cohort, of whom 51 706 (97.6%) received 2 doses of an mRNA COVID-19 vaccine and 474 (0.9%) reported a history of high-risk allergy. Individuals with vs without a history of high-risk allergy reported more allergic reactions after receiving dose 1 or 2 of the vaccine (11.6% [n = 55] vs 4.7% [n = 2461]). In the adjusted model, a history of high-risk allergy was associated with an increased risk of allergic reactions (adjusted relative risk [aRR], 2.46; 95% CI, 1.92-3.16), with risk being highest for hives (aRR, 3.81; 95% CI, 2.33-6.22) and angioedema (aRR, 4.36; 95% CI, 2.52-7.54).

Conclusions and relevance: This cohort study found that self-reported history of high-risk allergy was associated with an increased risk of self-reported allergic reactions within 3 days of mRNA COVID-19 vaccination. However, reported allergy symptoms did not impede the completion of the 2-dose vaccine protocol among a cohort of eligible health care employees, supporting the overall safety of mRNA COVID-19 vaccine.