Understanding the impact of population heterogeneity on the spread of vaccine-preventable diseases is crucial for containment and control. Here, we develop an experimental game model to examine how risks from disease and vaccination shape vaccination decisions in a population with heterogeneous vulnerability. We provide a full theoretical analysis of the game including a formula for Nash equilibrium. We hypothesize that overall vaccination rates will be higher for highly transmissible diseases and amongst the most vulnerable individuals. We then perform a series of experiments to confirm that our theoretical predictions and hypotheses agree with experimental results. Our results show that participants vaccinate strategically inline with Nash equilibrium. Specifically, vaccination rates were higher among more vulnerable individuals than among those less vulnerable. Additionally, we observed minimax behavior in a subset of individuals who consistently chose the secure option (vaccination) regardless of others’ actions. These findings underscore the epidemiological interdependence of vaccination decisions and the need for public health approaches that recognize the different risks and costs faced by vulnerable groups.