Acute allergic reactions to messenger RNA (mRNA) vaccines are rare but may limit public health immunization efforts. To characterize suspected allergic reactions to the first dose of coronavirus disease 2019 (COVID-19) mRNA vaccine and to assess the safety and utility of a two-step graded-dose protocol for the second dose of the Pfizer-BioNTech vaccine in patients with a history of low suspicion of anaphylaxis to their first dose. This was a retrospective evaluation of referrals to the allergy and immunology clinic for a presumed allergic reaction to the first dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna) between December 17, 2020, and February 28, 2021. Recommendations for the second dose and outcomes were evaluated by trained board-certified allergists. Seventy-seven patients presented with a Pfizer-BioNTech reaction (56 [72.7%]) or with a Moderna reaction (21 [27.3%]). Most patients (69.7%) had symptom onset within 4 hours. Most commonly reported symptoms were cutaneous (51.9%), cardiovascular (48.1%), and respiratory (33.8%) symptoms. Recommendations included to proceed with the single dose (70.1%), two-step graded dose (19.5%), or deferral (10.4%). Twelve of 15 patients completed the second dose with a graded-dose protocol. Of these patients, five reported at least one or more similar symptoms as experienced with their first dose. Of the patients with presumed allergic reactions to their first dose of COVID-19 mRNA vaccine, most were able to safely receive the second dose. For those with a low suspicion of anaphylaxis, the two-step graded protocol with the Pfizer-BioNTech vaccine was well tolerated. A graded-dose protocol could be an effective strategy for second-dose vaccination in those who may otherwise defer the second dose.