Objective: Stroke is a leading cause of long-term disability in the United States. Family caregivers are susceptible to negative outcomes as a result of their caregiving role. A stress process model was utilized to identify characteristics of stroke caregivers who are at risk for poor physical and mental health-related quality of life (QOL). Research Method: Individuals who experienced an incident stroke event within the previous year were identified from a larger epidemiologic study of stroke incidence. These stroke survivors were enrolled in the Caring for Adults Recovering from the Effects of Stroke (CARES) study along with their primary family caregivers (N = 146 dyads). Caregivers completed a baseline telephone interview that assessed physical and mental health-related QOL, problems their family members were experiencing, appraisals of those problems, and caregiver resources. Results: Objective stressors, appraisals, and caregiver resources were related to caregiver physical and mental health-related QOL, ps <.05. Objective stressors were found to have a stronger association with caregiver mental health than physical health. Hierarchical regression models showed the relative importance of each category of predictors. In the final models, older age and receiving more support were associated with worse physical health-related QOL whereas African American race and fewer stroke survivor problems were associated with better mental health. Conclusions: The correlates of health-related QOL identified in this national sample of caregivers can help identify stroke caregivers who are at risk for poor adjustment to the caregiving role and aid in identifying areas that can potentially be intervened upon for these caregivers. © 2013 American Psychological Association.