This study examined the quality of life correlates of family caregiving and caregiving strain in a large national epidemiological sample. Structured telephone interviews were conducted with 43,099 participants as part of the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Participants completed the 12-item short form health survey (SF-12) and brief measures of depressive symptoms, social contacts, and caregiving strain. Family caregiving responsibilities were reported by 12% of participants. Caregivers reported more quality of life problems than noncaregivers, but these effects were largely dependent on the perceived level of caregiving strain. High strain caregivers reported more problems with emotional distress, worse physical functioning, and fewer social contacts than noncaregivers. Conversely, caregivers who reported no strain from caregiving reported better quality of life than noncaregivers. Caregiving strain effects were not due to demographic differences or to more objective indicators of caregiving demand. Psychological and social indices of quality of life indicate prevalent problems among family caregivers who have experienced high strain from their caregiving responsibilities. Public health programs for disabled individuals should include assessments of strain on family caregivers and support services for those who report high levels of caregiving strain. © 2009 Springer Science+Business Media B.V.