BackgroundGeneral vaccination rates have been falling globally despite unequivocal health benefits. Noncompliance can result from access barriers and/or hesitant attitudes. Few studies have investigated the prevalence and determinants of noncompliance with COVID‐19 vaccination in blood donors.MethodsWe surveyed blood donors on COVID‐19 infection and vaccination history, barriers and motivations for COVID‐19 vaccination, and comorbidities. We estimate the prevalence of noncompliance, the prevalence of hesitancy toward COVID‐19 vaccines, and investigate associated factors using multivariable models.ResultsFrom December 2021 to December 2022, 33,610 survey respondents were included. Of these, 24% had not been vaccinated for COVID‐19 or had missing vaccination information, and 99% of those who reported reasons for being unvaccinated declared at least one of three hesitant attitudes presented in the survey (safety concerns; personal/cultural/religious beliefs; being young and not worrying about being vaccinated). Among noncompliant donors, <2% reported access barriers. In the multivariable model addressing factors associated with vaccine noncompliance, younger age, male gender, White/Caucasian race, absence of comorbidities, residency in a State with less restrictive COVID‐19 policies, and living in micropolitan or rural areas were identified as significant predictors. Younger age and White/Caucasian race were independently associated with vaccine hesitancy among noncompliant donors.ConclusionsWe found high rates of noncompliance with COVID‐19 vaccination in blood donors, mostly driven by vaccine hesitancy. Understanding vaccine adherence among blood donors—a relatively highly educated and healthy population, with good healthcare access and usually motivated by altruism—could provide key information on determinants of vaccine noncompliance that may be harder to overcome.