PURPOSE: In order to better understand how family caregiving may contribute to poor health outcomes, this study sought to determine (1) if and to what extent caregiving characteristics were associated with caregiver strain and health-related quality of life (HRQoL), and (2) whether caregiver strain mediated this association. METHODS: Data were from the 2008-2010 Survey of the Health of Wisconsin, a representative sample of Wisconsin adults aged 21-74 years. Participants completed questionnaires about their caregiving, sociodemographics, and HRQoL; 264 caregivers were identified. Staged generalized additive models assessed the associations among caregiving characteristics, caregiver strain, and HRQoL; survey weights were applied to account for the complex sampling design. RESULTS: More hours per week of care and greater duration of caregiving were associated with higher levels of strain. Greater caregiver strain was in turn associated with worse mental HRQoL. However, most caregiving characteristics were not directly associated with mental or physical HRQoL. CONCLUSIONS: The findings suggest a chains-of-risk model in which caregiving may increase strain, which may in turn adversely influence mental HRQoL. Using this perspective to refine interventions may improve our ability to support caregivers on practice and policy levels.