Numerous recent studies have found that overweight adults experience lower overall mortality than those who are underweight, normal-weight, or obese. These highly publicized findings imply that overweight may be the optimal weight category for overall health via its association with longevity-a conclusion with important public health implications. In this study, the authors examined the association between body mass index (BMI; (weight (kg)/height (m)(2))) and 3 markers of health risks using a nationally representative sample of US adults aged 20-80 years (n = 9,255) from the National Health and Nutrition Examination Survey (2005-2008). Generalized additive models, a type of semiparametric regression model, were used to examine the relations between BMI and biomarkers of inflammation, metabolic function, and cardiovascular function (C-reactive protein, hemoglobin A(1c), and high density lipoprotein cholesterol, respectively). The association between BMI and each biomarker was monotonic, with higher BMI being consistently associated with worse health risk profiles at all ages, in contrast to the U-shaped relation between BMI and mortality. Prior results suggesting that the overweight BMI category corresponds to the lowest risk of mortality may not be generalizable to indicators of health risk.