BackgroundCurrent concerns about vaccination resistance often cite the Internet as a source of vaccine controversy. Most academic studies of vaccine resistance online use quantitative methods to describe misinformation on vaccine-skeptical websites. Findings from these studies are useful for categorizing the generic features of these websites, but they do not provide insights into why these websites successfully persuade their viewers. To date, there have been few attempts to understand, qualitatively, the persuasive features of provaccine or vaccine-skeptical websites.ObjectiveThe purpose of this research was to examine the persuasive features of provaccine and vaccine-skeptical websites. The qualitative analysis was conducted to generate hypotheses concerning what features of these websites are persuasive to people seeking information about vaccination and vaccine-related practices.MethodsThis study employed a fully qualitative case study methodology that used the anthropological method of thick description to detail and carefully review the rhetorical features of 1 provaccine government website, 1 provaccine hospital website, 1 vaccine-skeptical information website focused on general vaccine safety, and 1 vaccine-skeptical website focused on a specific vaccine. The data gathered were organized into 5 domains: website ownership, visual and textual content, user experience, hyperlinking, and social interactivity.ResultsThe study found that the 2 provaccine websites analyzed functioned as encyclopedias of vaccine information. Both of the websites had relatively small digital ecologies because they only linked to government websites or websites that endorsed vaccination and evidence-based medicine. Neither of these websites offered visitors interactive features or made extensive use of the affordances of Web 2.0. The study also found that the 2 vaccine-skeptical websites had larger digital ecologies because they linked to a variety of vaccine-related websites, including government websites. They leveraged the affordances of Web 2.0 with their interactive features and digital media.ConclusionsBy employing a rhetorical framework, this study found that the provaccine websites analyzed concentrate on the accurate transmission of evidence-based scientific research about vaccines and government-endorsed vaccination-related practices, whereas the vaccine-skeptical websites focus on creating communities of people affected by vaccines and vaccine-related practices. From this personal framework, these websites then challenge the information presented in scientific literature and government documents. At the same time, the vaccine-skeptical websites in this study are repositories of vaccine information and vaccination-related resources. Future studies on vaccination and the Internet should take into consideration the rhetorical features of provaccine and vaccine-skeptical websites and further investigate the influence of Web 2.0 community-building features on people seeking information about vaccine-related practices.