To determine optimal threshold values for body mass index (BMI) and waist circumference (WC) for detecting cardiovascular disease (CVD) risk (as defined with >/=3 CVD risk factors [RFs]) in adolescents. The 1999-2004 National Health and Nutrition Examination Surveys (NHANES) cross-sectional data for 12- to 19-year-old adolescents (n = 2581) was analyzed. Main outcome measures were >/=3 age-adjusted CVD RFs (high- and low-density lipoprotein cholesterol level, triglyceride level, glucose level, insulin level, and systolic and diastolic blood pressure). The presence of >/=3 RFs was predicted from age- and sex-adjusted BMI and WC values with receiver operating characteristics analyses. The proportion of adolescents at risk for >/=3 RFs ranged from 17% to 19%. Both BMI and WC had good diagnostic accuracy, ranging from 0.73 to 0.83, and good sensitivity and specificity, ranging from 0.68 to 0.77. The BMI cutoff points ranged from 19.5 to 25.0 kg/m(2) for boys and from 19.4 to 27.0 kg/m(2) for girls, and WC cutoff points ranged from 66.8 to 87.5 cm for boys and from 71.5 to 87.2 cm for girls. Age-, sex-, and ethnicity/race-specific threshold values for BMI and WC may have significant clinical usefulness in identifying adolescents and teenagers at risk for later CVD onset.