This study examines whether frailty is associated with mortality independently of physiological dysregulation (PD) and, if so, which is the more accurate predictor of survival. Data come from the Social Environment and Biomarkers of Aging Study. We use Cox proportional hazard models to test the associations between PD, frailty, and 4- to 5-year survival. We use Harrell’s concordance index to compare predictive accuracy of the models. Both PD and frailty are significantly, positively, and independently correlated with mortality: Worse PD scores and being frail are associated with a higher risk of dying. The overall PD score is a more accurate predictor of survival than frailty, although model prediction improves when both measures are included. PD and frailty independently predict mortality, suggesting that the two measures may be capturing different aspects of the same construct and that both may be important for identifying individuals at risk for adverse health outcomes.