Objective: This study considers whether rural status or living in a particular region of the United States has effects on mental and physical health. The analyses examine whether there are independent and interactive effects of rural status and region of residence on health, beyond individual level factors related to poverty. Methods:Ordinary least squares (OLS) regression models are used to examine the relationships between rural and regional residence and health across three time periods. Results: Negative health effects of rural residence were found only in the South region. Positive health effects of rural residence were found only in the Midwest region. There are no observed health risks associated with rural or regional residence across group. Discussion: The results indicate a cumulative risk of rural and Southern residence for older men and women. Living in a rural place in the midwestern United States seems to provide unique sources of health benefits.