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Introduction: Twitter and media coverage on poliomyelitis help maintain global support for its eradication., Objective: To test our hypothesis that themes of polio-related tweets and media articles would differ by location of interest (hashtag of country name mentioned in the tweet; country name mentioned in media articles) but would be similar to each other (tweets and media articles) for each location of interest., Methods: We retrospectively examined a 40% random sample of Twitter data containing the hashtag #polio from January 1, 2014, to April 30, 2015 (N = 79,333), from which we extracted 5 subcorpora each with a co-occurring hashtag #India (n = 5027), #Iraq (n = 1238), #Nigeria (n = 1364), #Pakistan (n = 11,427), and #Syria (n = 2952). We also retrieved and categorized 73 polio-related English-language news stories from within the same timeframe. We assessed the association between polio-related English news themes and the Twitter content. Descriptive analyses and unsupervised machine learning (latent Dirichlet allocation modeling) were conducted on the 5 Twitter subcorpora., Results: The results of the latent Dirichlet allocation modeling on the specific subcorpora with country co-occurring hashtags showed significant differences between the 5 countries in terms of content. English mass media content focused largely on violence/conflicts and cases of polio, whereas social media focused on eradication and vaccination efforts along with celebrations., Discussion: Contrary to our hypothesis, our evidence suggests Twitter content differs significantly from English mass media content. Evidence from our study helps inform media monitoring and communications surveillance during global public health crises, such as infectious disease outbreaks, as well as reactions to health promotion campaigns.