Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30-102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988-1994. During a 12-year follow-up (102,172 person-years), 1,188 men and 925 women died. In multivariable-adjusted analyses, waist-to-thigh ratio (WTR) in both sexes (Ptrend<0.01 for both) and waist-to-hip ratio (WHR) in women (Ptrend 0.001) were positively associated with mortality in middle-aged adults (30-64 years), while BMI and waist circumference (WC) exhibited U- or J-shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5-24.9 kg/m2) and obese (BMI>or=30.0 kg/m2) adults. In older adults (65-102 years), a higher BMI in both sexes (Ptrend<0.05) and WC in men (Ptrend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle-aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.