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The COVID-19 vaccine was initially offered to frontline health care workers (HCWs), due to the high risk of contracting COVID-19 through occupational exposure to patients. Low HCW vaccine uptake can impact overall community-level vaccine uptake. This study used the Diffusion of Innovation (DOI) Theory to understand factors related to COVID-19 vaccine uptake in HCWs. We surveyed Pennsylvanian HCWs (excluding Philadelphia) from August 2022 to February 2023. Survey questions inquired about demographics, COVID-19 vaccination status, reasons for receiving/declining the COVID-19 vaccine, and sources of information about the vaccine. Participants (n = 3,490) were 85% female, 89% White, and 93% (n = 3,255) reported receiving at least one dose of a COVID-19 vaccine. HCWs were categorized into adopter categories of the DOI Theory: innovators (56%), early adopters (9%), early majority (11%), late majority (7%), and laggards (17%). The major reason that prompted participants to get the vaccine was to protect them against COVID-19 infection (78%), while the major reason for declining the vaccine was due to concern about possible side effects from the vaccine (78%). We applied the DOI Theory to characterize adopters and identify factors related to COVID-19 vaccine uptake in HCWs. As updated COVID-19 vaccines are approved for the United States market, our findings may be used to improve vaccine education and communication among HCWs to support vaccine uptake. • The Diffusion of Innovation Theory was used to characterize COVID-19 vaccine uptake. • Most health care workers were categorized as innovators and early adopters. • Factors related to COVID-19 vaccine uptake vary by category of adoption. [ABSTRACT FROM AUTHOR]