High whole-body fat percentage is independently associated with increased mortality. We aimed to identify a simple anthropometric linear equation that is more accurate than the body mass index (BMI) to estimate whole-body fat percentage among adult individuals. National Health and Nutrition Examination Survey (NHANES) 1999-2004 data (n = 12,581) were used for model development and NHANES 2005-2006 data (n = 3,456) were used for model validation. From the 365 anthropometric indices generated, the final selected equation was as follows: 64 - (20 × height/waist circumference) + (12 × sex), named as the relative fat mass (RFM); sex = 0 for men and 1 for women. In the validation dataset, compared with BMI, RFM better predicted whole-body fat percentage, measured by dual energy X-ray absorptiometry (DXA), among women and men. RFM showed better accuracy than the BMI and had fewer false negative cases of body fat-defined obesity among women and men. RFM reduced total obesity misclassification among all women and all men and, overall, among Mexican-Americans, European-Americans and African-Americans. In the population studied, the suggested RFM was more accurate than BMI to estimate whole-body fat percentage among women and men and improved body fat-defined obesity misclassification among American adult individuals of Mexican, European or African ethnicity.