<p><b>CONTEXT: </b>US Hispanic/Latino youth are disproportionally affected by the obesity and diabetes.</p><p><b>OBJECTIVE: </b>We examined associations of adiposity measures with insulin resistance (IR) and hyperglycemia and the influences of sex and pubertal development on these associations.</p><p><b>DESIGN, SETTING, AND PARTICIPANTS: </b>We performed a cross-sectional analysis of 1223 8- to 16-year-old Hispanic/Latino youth from a community-based study in the United States (SOL Youth).</p><p><b>MAIN OUTCOME MEASURES: </b>We measured IR (≥75th percentile of sex-specific Homeostatic Model Assessment of Insulin Resistance) and hyperglycemia (fasting glucose ≥100 mg/dL or hemoglobin a1c ≥5.7%).</p><p><b>RESULTS: </b>In boys, body mass index (BMI) showed the strongest association with IR [prevalence ratio (PR), 2.10; 95% confidence interval (CI), 1.87 to 2.36 per standard deviation], which was not statistically different compared with body fat percentage (%BF) (PR, 2.03; 95% CI, 1.81 to 2.29) and waist circumference (WC) (PR, 1.89; 95% CI, 1.67 to 2.13) but was significantly stronger compared with fat mass index (FMI) (PR, 1.79; 95% CI, 1.63 to 1.96), waist-to-hip ratio (WHR) (PR, 1.32; 95% CI, 1.21 to 1.44), and waist-to-height ratio (WHtR) (PR, 1.76; 95% CI, 1.54 to 2.01) (P for difference, <0.05). In girls, %BF (PR, 2.73; 95% CI, 2.34 to 3.20) showed a significantly stronger association with IR compared with BMI (PR, 1.48; 95% CI, 1.29 to 1.70), FMI (PR, 1.71; 95% CI, 1.49 to 1.95), WC (PR, 1.96; 95% CI, 1.70 to 2.27), WHR (PR, 1.95; 95% CI, 1.70 to 2.23), and WHtR (PR, 1.79; 95% CI, 1.53 to 2.09) (P for difference, <0.003). Associations between adiposity measures and IR were generally stronger among children in puberty versus those who had completed puberty, with significant interactions for WC and WHtR in boys and for BMI in girls (P for interaction, <0.01). Adiposity measures were modestly associated with hyperglycemia (PR, 1.14 to 1.25), with no interactions with sex or pubertal status.</p><p><b>CONCLUSIONS: </b>Sex and puberty may influence associations between adiposity measures and IR in US Hispanic/Latino youth. Multiple adiposity measures are needed to better assess IR risk between boys and girls according to pubertal status.</p>