Lyme disease (LD) cases in the United States are estimated to be approaching 500,000 annually. Protective measures, such as repellent use and wearing protective clothing are recommended by public health officials. However, no protective measure has been proven to be consistently effective, partly because they require consistent and persistent behaviour change. While safe and effective vaccines are in development, it is unclear what factors influence the intention to vaccinate against LD. This study uses the Health Belief Model (HBM) framework to determine key drivers associated with vaccine intention. The HBM is widely applied in public health research and uses the following constructs: perceived susceptibility and severity of disease, perceived benefits and barriers to disease prevention, and cues to action for disease prevention to predict health behaviours. To date, the HBM framework has not been applied to vaccination intention for LD. Data were collected from 874 adults and 834 caregivers of children residing in US states endemic to LD. Sampling adults and caregivers allows us to explore how the intention to vaccinate differs among those at-risk. Estimates from structural equation modelling (SEM) show that the HBM constructs explain much of the variation in intention to vaccinate against LD. Both adult and caregiver intentions to vaccinate are positively influenced by cues to action, perceived susceptibility of LD, and perceived benefits to vaccination. However, there is variation in the influence of constructs across the samples. Caregiver's intention to vaccinate is positively influenced by the perceived severity of LD and negatively influenced by safety concerns about the vaccine, whereas adult intention is negatively influenced by perceived barriers to vaccination. A strong relationship of cues to action on vaccine intention in samples of adults and caregivers suggests the importance of a recommendation from a healthcare provider or the Centers for Disease Control and Prevention (CDC).