This study aims to compare the performance of body mass index (BMI), waist circumference (WC), and waist-to-height-ratio (WHtR) to predict the presence of at least 3 main CV risk factors in US adolescents. A total of 3621 adolescents (boys: 49.9%) aged 12-17 years from the US National Health and Nutrition Examination Survey (1999-2012) were included in this study. Measured CV risk factors included systolic/diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting plasma glucose. The AUC of BMI-z score, WC-z score and WHtR-z score to predict at least three CV risk factors were similar (~0.85), irrespective of criteria used to define abnormal levels of CV risk factors. A 1-SD increase in any of three indices to predict CV risk was also similar for the three adiposity scores. For instance, a 1-SD increase risk in BMI-z score, WC-z score and WHtR-z score was 3.32 (95%CI 2.53-4.36), 3.43 (95%CI 2.64-4.46), and 3.45 (95%CI 2.64-4.52), respectively, in the total population using the International Diabetes Federation definition. In addition, the most efficient WHtR cut-off for screening CV risk was ~0.50 in US adolescents. In summary, BMI, WC and WHtR performed similarly well to predict the presence of at least 3 main CV risk factors among US adolescents.