Two messenger RNA (mRNA) vaccines (Pfizer-BioNTech and Moderna) encoding the spike protein of SARS-CoV-2 induce the production of spike antibodies that neutralize SARS-CoV-2 and are clinically effective against COVID-19. These vaccines can elicit greater local and systemic reactions in persons with prior SARS-CoV-2 infection. Whether symptoms following vaccination are associated with effectiveness is unknown, and, therefore, anxiety can arise in persons who did not develop a reaction following vaccination. We evaluated symptoms following vaccination and serum spike antibody levels in a cohort of hospital workers (HWs) who received either mRNA vaccine and had known status of prior SARS-CoV-2 infection to identify differences in symptoms and serum immunoglobulin G (IgG) antibodies against S1 spike protein.