To analyze factors associated with COVID-19 vaccine acceptance in Spain, over time. We used data from a national study that included 5 online surveys carried out every 2 months from September 2020 to May 2021. Each round recruited a sample of 1000 participants aged 18 years or older. We performed a multivariable logistic regression with vaccination acceptance as the dependent variable. We evaluated time trends through the interaction terms of each of the explanatory variables and the time. Vaccination acceptance increased from 43.1% in September 2020 to 84.5% in May 2021. Sex, age, concerns about disease severity, health services overload, and people not wearing a face mask, together with adherence to preventive behavior, health literacy, and confidence in scientists, health care professionals' information, and adequacy of governmental decisions, were variables associated with vaccination acceptance. In a changing situation, vaccine acceptance factors and time trends could help in the design of contextualized public health messages. It is important to strengthen the population's trust in institutions, health care professionals, and scientists to increase vaccination rates, as well as to ensure easy access to accurate information for those who are more reluctant. (. 2022;112(11):1611-1619. https://doi.org/10.2105/AJPH.2022.307039).
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