The American Heart Association's Life's Simple 7 initiative allows individuals to assess health factors (BP, cholesterol, and glucose) and health behaviors (cigarette smoking, physical activity, diet, and body mass index) to promote improved cardiovascular health. Because several cardiovascular risk factors also associate with progressive kidney disease, Life's Simple 7 may also inform an individual's risk for ESRD. Here, we investigated the association of Life's Simple 7 components with both ESRD incidence and all-cause mortality among 3093 participants with an estimated GFR (eGFR) <60 ml/min per 1.73 m(2) from the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. During a median 4 years of follow-up, 160 participants developed ESRD, and 610 participants died. Compared with individuals who had zero or one of the Life's Simple 7 components in the ideal range, those individuals with two, three, and four ideal factors had progressively lower risks for ESRD; furthermore, no participant with five to seven ideal factors developed ESRD. The risk for all-cause mortality exhibited a similar trend. Adjusting for eGFR and albuminuria, however, completely attenuated the associations between the number of ideal factors and the risks for both ESRD and all-cause mortality. In conclusion, a favorable cardiovascular risk profile among individuals with CKD associates with a reduced risk for ESRD and mortality, but whether the severity of kidney disease confounds or mediates this association requires additional investigation.