BACKGROUND: The sensation of throat closure after vaccination is concerning for anaphylaxis and leads to vaccine hesitancy. OBJECTIVES: We characterized patients who developed laryngopharyngeal symptoms (LPhS) after coronavirus disease 2019 (COVID-19) vaccination and assessed risk factors for these symptoms. METHODS: The study analyzed data from the COVID-19 vaccines adverse reactions registry (December 14, 2020, to June 13, 2022). Outcomes included the incidence of postvaccination LPhS and use of epinephrine. We identified and compared risk factors for COVID-19 postvaccination reactions between subjects with and without LPhS. RESULTS: A total of 158 subjects were enrolled onto the registry. LPhS were reported in 61 subjects (38.6%), of whom 52 (85.2%) received a subsequent dose. With initial vaccination, the use of epinephrine was higher in subjects with LPhS (20%) compared to those without (6%;  = .0094). Fifty-two subjects (85.2%) with LPhS received a subsequent COVID-19 vaccine dose with milder or no symptoms, and none needed treatment with epinephrine. Those with LPhS were more likely to have a history of drug allergies ( = .02), severe medication allergies ( = .03), gastroesophageal reflux disease ( = .018), and need for antireflux medications ( = .0085) compared to controls. CONCLUSIONS: In our registry, postvaccination LPhS were common. LPhS can mimic anaphylaxis and lead to more frequent use of epinephrine. Gastroesophageal reflux disease was more frequent in these subjects. Patients with subjective throat closure sensation can safely receive subsequent vaccine doses with close observation and reassurance. LPhS are not unique to COVID-19 vaccines. Patient and provider education regarding the role of gastroesophageal reflux disease as a risk factor for LPhS with vaccination can improve vaccine uptake.