To understand how Twitter accounts operated by the Russian Internet Research Agency (IRA) discussed vaccines to increase the credibility of their manufactured personas. We analyzed 2.82 million tweets published by 2689 IRA accounts between 2015 and 2017. Combining unsupervised machine learning and network analysis to identify “thematic personas” (i.e., accounts that consistently share the same topics), we analyzed the ways in which each discussed vaccines. We found differences in volume and valence of vaccine-related tweets among 9 thematic personas. Pro-Trump personas were more likely to express antivaccine sentiment. Anti-Trump personas expressed support for vaccination. Others offered a balanced valence, talked about vaccines neutrally, or did not tweet about vaccines. IRA-operated accounts discussed vaccines in manners consistent with fabricated US identities. IRA accounts discussed vaccines online in ways that evoked political identities. This could exacerbate recently emerging partisan gaps relating to vaccine misinformation, as differently valenced messages were targeted at different segments of the US public. These sophisticated targeting efforts, if repeated and increased in reach, could reduce vaccination rates and magnify health disparities. (. Published online ahead of print March 19, 2020: e1-e7. doi:10.2105/AJPH.2019.305564).