OBJECTIVE: To validate fasting indexes against minimal model analysis (MMOD) of the frequently sampled intravenous glucose tolerance test (FSIVGTT) in an obese pediatric population. RESEARCH DESIGN AND METHODS: FSIVGTT-MMOD results were compared with homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin with the sample stratified by sex, puberty, and sensitivity index (S(i)) median in 191 children (82 males and 109 females, 13.9 +/- 2.9 years of age, BMI 36.9 +/- 6.2 kg/m(2), BMI SD score 6.1 +/- 1.6). RESULTS: Across pubertal groups, correlation coefficients between S(i) and HOMA-IR ranged from -0.43 to -0.78 in males and from -0.53 to -0.57 in females (age and BMI adjusted, P < 0.05 in all instances). Similar results were seen for fasting insulin. In females, the relationship was significantly weaker in more-insulin-resistant subjects. CONCLUSIONS: The validity of fasting indexes in explaining S(i) was sex dependent, varied with pubertal stage, and in females was influenced by degree of insulin sensitivity. In obese pediatric populations, we generally discourage the use of fasting indexes, although the validity varies within subgroups.