BACKGROUND: To determine the validity of body mass index (BMI) to identify excess fatness in youth with Down syndrome (DS). METHODS: Using the Centers for Disease Control and Prevention (CDC) growth reference, we defined overweight ( > = 85th percentile) and obesity ( > = 95th percentile) based on participants' age- and sex-specific BMI z-scores, calculated from measured height and weight. Percentage body fat was measured by dual-energy X-ray absorptiometry. We determined sensitivity, specificity, positive predictive value, negative predictive value and efficiency of BMI percentiles to identify excess adiposity relative to elevated percentage body fat cut-offs developed from the Pediatric Rosetta Body Composition project in 32 youth (20 boys/12 girls), ages 13-21 years with Down syndrome. RESULTS: For adolescents with Down syndrome using the cut-off points of 95th percentile for BMI (obesity), sensitivity and specificity were 71% and 96% respectively. Positive predictive value was 83% and negative predictive value was 92%. Overall efficiency was 91%. Sensitivity and specificity for BMI cut-offs above the 85th percentile (overweight) were 100% and 60% respectively. The positive predictive value was 41% and negative predictive value was 100%. Overall efficiency was 69%. CONCLUSION: On the whole, the obesity ( > = 95th percentile) cut-off performs better than the overweight cut-off (85th-94th percentile) in identifying elevated fatness in youth with DS. Wiley and Sons Ltd, MENCAP and IASSID.