Vaccination yields the direct individual benefit of protecting recipients from infectious diseases and also the indirect social benefit of reducing the transmission of infections to others, often referred to as herd immunity. This research examines how prosocial concern for vaccination, defined as people’s preoccupation with infecting others if they do not vaccinate themselves, motivates vaccination in more and less populated regions of the United States. A nationally representative, longitudinal survey of 2,490 Americans showed that prosocial concern had a larger positive influence on vaccination against influenza in sparser regions, as judged by a region’s nonmetropolitan status, lesser population density, and lower proportion of urban land area. Two experiments (total n = 800), one preregistered, provide causal evidence that drawing attention to prosocial (vs. individual) concerns interacted with social density to affect vaccination intentions. Specifically, prosocial concern led to stronger intentions to vaccinate against influenza and COVID-19 but only when social density was low (vs. high). Moderated mediation analyses show that, in low-density conditions, the benefits of inducing prosocial concern were due to greater perceived impact of one’s vaccination on others. In this light, public health communications may reap more benefits from emphasizing the prosocial aspects of vaccination in sparser environments.