OBJECTIVES: Using a large, national sample, this study examined perceived caregiving strain and other caregiving factors in relation to all-cause mortality. METHOD: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is a population-based cohort of men and women aged 45 years and older. Approximately 12% (n = 3,710) reported that they were providing ongoing care to a family member with a chronic illness or disability. Proportional hazards models were used for this subsample to examine the effects of caregiving status measures on all-cause mortality over the subsequent 5-year period, both before and after covariate adjustment. RESULTS: Caregivers who reported high caregiving strain had significantly higher adjusted mortality rates than both no strain (hazard ratio [HR] = 1.55, p = .02) and some strain (HR = 1.83, p = .001) caregivers. The mortality effects of caregiving strain were not found to differ by race, sex, or the type of caregiving relationship (i.e., spouse, parent, child, sibling, and other). DISCUSSION: High perceived caregiving strain is associated with increased all-cause mortality after controlling for appropriate covariates. High caregiving strain constitutes a significant health concern and these caregivers should be targeted for appropriate interventions.