While metaphors are frequently used to address misconceptions and hesitancy about vaccines, it is unclear how effective they are in health messaging. Using a between-subject, pretest/posttest design, we investigated the impact of explanatory metaphors on people’s attitudes toward vaccines. We recruited participants online in the US (N = 301) and asked them to provide feedback on a (fictional) health messaging campaign, which we organized around responses to five common questions about vaccines. All participants completed a 24-item measure of their attitudes towards vaccines before and after evaluating the responses to the five questions. We created three possible response passages for each vaccine question: two included extended explanatory metaphors, and one contained a literal response (i.e., no explanatory metaphors). Participants were randomly assigned to receive either all metaphors or all ‘literal’ responses. They rated each response on several dimensions and then described how they would answer the target question about vaccines if it were posed by a friend. Results showed participants in both conditions rated most messages as being similarly understandable, informative, and persuasive, with a few notable exceptions. Participants in both conditions also exhibited a similar small—but significant—increase in favorable attitudes towards vaccines from pre- to posttest. Notably, participants in the metaphor condition provided longer free-response answers to the question posed by a hypothetical friend, with different metaphors being reused to different extents and in different ways in their responses. Taken together, our findings suggest that: (a) Brief health messaging passages may have the potential to improve attitudes towards vaccines, (b) Metaphors neither enhance nor reduce this attitude effect, (c) Metaphors may be more helpful than literal language in facilitating further social communication about vaccines.