Objective: Information exchange via Twitter and other forms of social media make public health communication more complex as citizens play an increasingly influential role in shaping acceptable or desired health behaviors. Taking the case of the 2009–2010 H1N1 pandemic, we explore in detail the dissemination of H1N1-related advice in the UK through Twitter to see how it was used to discourage or encourage vaccine and antiviral uptake. Methods: In three stages we conducted (1) an analysis of general content, retweeting patterns, and URL sharing, (2) a discourse analysis of the public evaluation of press releases and (3) a template analysis of conversations around vaccine and antiviral uptake, using Protection Motivation Theory (PMT) as a way of understanding how the public weighed the costs and benefits. Results: Network analysis of retweets showed that information from official sources predominated. Analysing the spread of significant messages through Twitter showed that most content was descriptive but there was some criticism of health authorities. A detailed analysis of responses to press releases revealed some scepticism over the economic beneficiaries of vaccination, that served to undermine public trust. Finally, the conversational analysis showed the influence of peers when weighing up the risks and benefits of medication. Conclusion: Most tweets linked to reliable sources, however Twitter was used to discuss both individual and health authority motivations to vaccinate. The PMT framework describes the ways individuals assessed the threat of the H1N1 pandemic, weighing this against the perceived cost of taking medication. These findings offer some valuable insights for social media communication practices in future pandemics.