Quantification of lean body mass and fat mass can provide important insight into epidemiological research. However, there is no consensus on generalisable anthropometric prediction equations to validly estimate body composition. We aimed to develop and validate practical anthropometric prediction equations for lean body mass, fat mass and percent fat in adults (men, n 7531; women, n 6534) from the National Health and Nutrition Examination Survey 1999–2006. Using a prediction sample, we predicted each of dual-energy X-ray absorptiometry (DXA)-measured lean body mass, fat mass and percent fat based on different combinations of anthropometric measures. The proposed equations were validated using a validation sample and obesity-related biomarkers. The practical equation including age, race, height, weight and waist circumference had high predictive ability for lean body mass (men: R 2=0·91, standard error of estimate (SEE)=2·6 kg; women: R 2=0·85, SEE=2·4 kg) and fat mass (men: R 2=0·90, SEE=2·6 kg; women: R 2=0·93, SEE=2·4 kg). Waist circumference was a strong predictor in men only. Addition of other circumference and skinfold measures slightly improved the prediction model. For percent fat, R 2 were generally lower but the trend in variation explained was similar. Our validation tests showed robust and consistent results with no evidence of substantial bias. Additional validation using biomarkers demonstrated comparable abilities to predict obesity-related biomarkers between direct DXA measurements and predicted scores. Moreover, predicted fat mass and percent fat had significantly stronger associations with obesity-related biomarkers than BMI did. Our findings suggest the potential application of the proposed equations in various epidemiological settings.