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BackgroundVaccine hesitancy could undermine the effectiveness of COVID-19 vaccination programs. Knowledge about people’s lived experiences regarding COVID-19 vaccination can enhance vaccine promotion and increase uptake.AimTo use COVID-19 vaccine trial participants’ experiences to identify key themes in the lived experience of vaccination early in the vaccine approval and distribution process.MethodsWe interviewed 31 participants in the Iowa City, Iowa US site of the Pfizer/BioNTech COVID-19 vaccine phase 3 clinical trial. While trial participation differs from clinical receipt of an approved vaccine in key ways, it offers the first view of people’s lived experiences of potentially receiving a COVID-19 vaccine. The trial context is also useful since decision-making about vaccination and medical research participation often involve similar hopes and concerns, and because the public appears to view even approved COVID-19 vaccines as experimental given their novelty. Semi-structured interviews addressed subjects’ experiences, including decision-making and telling others about their trial participation. We analyzed verbatim transcripts of these interviews thematically and identified common themes relevant for vaccination decision-making.ResultsParticipants across demographic groups, including age, sex/gender, race/ethnicity, and political affiliation, described largely similar experiences. Key motivations for participation included ending the pandemic/restoring normalcy, protecting oneself and others, doing one’s duty, promoting/modeling vaccination, and expressing aspects of identity like being a helper, career-related motivations, and support of science/vaccines. Participants often felt uniquely qualified to help via trial participation due to personal attributes like health, sex/gender or race/ethnicity. They reported hearing concerns about side effects and the speed and politicization of vaccine development. Participants responded by normalizing and contextualizing side effects, de-politicizing vaccine development, and explaining how the rapid development process was nevertheless safe.ConclusionThese findings regarding participants’ reported motivations for trial participation and interactions with concerned others can be incorporated into COVID-19 vaccine promotion messaging aimed at similar populations.