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BackgroundAcceptance rates of COVID-19 vaccines have still not reached the required threshold to achieve herd immunity. Understanding why some people are willing to be vaccinated and others are not is a critical step to develop efficient implementation strategies to promote COVID-19 vaccines. ObjectiveWe conducted a theory-based content analysis based on the capability, opportunity, motivation–behavior (COM-B) model to characterize the factors influencing behavioral intentions toward COVID-19 vaccines mentioned on the Twitter platform. MethodsWe collected tweets posted in English from November 1-22, 2020, using a combination of relevant keywords and hashtags. After excluding retweets, we randomly selected 5000 tweets for manual coding and content analysis. We performed a content analysis informed by the adapted COM-B model. ResultsOf the 5000 COVID-19 vaccine–related tweets that were coded, 4796 (95.9%) were posted by unique users. A total of 97 tweets carried positive behavioral intent, while 182 tweets contained negative behavioral intent. Of these, 28 tweets were mapped to capability factors, 155 tweets were related to motivation, 23 tweets were related to opportunities, and 74 tweets did not contain any useful information about the reasons for their behavioral intentions (κ=0.73). Some tweets mentioned two or more constructs at the same time. Tweets that were mapped to capability (P |