Background: Rural family caregivers experience high levels of stress, burden, and psychological distress related to caregiving and are at higher risk for cardiovascular disease (CVD) compared to non-caregivers. Health activation (known also as patient activation) is an indicator of engagement in self-care and is defined as an individual’s knowledge, skill, and confidence in managing health. Better health activation is associated with better health outcomes. Because rural individuals are at greater risk of CVD and have fewer supportive resources than those in urban environments, we wanted to determine the relationship of health activation with risk for future CVD in this population. Objective: The purpose of this study was to examine the association of health activation with risk for future CVD among rural family caregivers of patients with chronic illness. Methods: This was a cross-sectional study using baseline data from a randomized controlled trial of an intervention to reduce CVD risk for rural caregivers. We measured health activation using the Patient Activation Measure. The predicted10-year risk of CVD was assessed using the Framingham risk score. Covariates potentially related to cardiovascular risks among caregivers were collected including stress (Perceived Stress Scale-Cohen), anxiety (Brief Symptom Inventory), depressive symptoms (Patient Health Questionnaire-9), and caregiver burden (Zarit Burden Interview). Generalized linear regression was used to analyze data. Results: Of 217 caregivers (mean age 53 ± 13 years, 79% female), 48% were caring for a spouse, 20% were caring for a parent, and the remaining 32% were caring for a sibling, a child, or other relatives. Caregivers with higher health activation had a lower risk of developing CVD in the future based on their Framingham risk score (B = -0.081, SE= 0.039, 95% CI= -0.158 to -0.004, p=0.038), independent of the other covariates. Every 10-point increase in health activation score was associated with a nearly 1-point (0.81) decrease in Framingham risk score. Conclusions: Health activation is a good predictor of future risk for developing CVD. Development and testing of interventions to promote health activation before people develop CVD is suggested to decrease the risk of future CVD.