Technical Abstract: We examined the effects of a multicomponent, school-based program, addressing risk factors for diabetes among children whose race, or ethnic group and socioeconomic status placed them at high risk for obesity and type 2 diabetes. Using a cluster design, we randomly assigned 42 schools to either a multicomponent school-based intervention (21 schools), or assessment only (control) (21 schools). A total of 4603 students participated (mean [+-SD] age, 11.3+-0.6 years; 54.2% Hispanic and 18.0% black; 52.7% girls). At the beginning of 6th grade and the end of 8th grade, students underwent measurements of body-mass index (BMI), waist circumference, and fasting glucose and insulin levels. There was a decrease in the primary outcome, the combined prevalence of overweight and obesity, in both the intervention and control schools, with no significant difference between the school groups. The intervention schools had greater reductions in the secondary outcomes of BMI z score, percentage of students with waist circumference at or above the 90th percentile, fasting insulin levels (P = 0.04 for all comparisons), and prevalence of obesity (P = 0.05). Similar findings were observed among students who were at or above the 85th percentile for BMI at baseline. Less than 3% of the students who were screened had an adverse event; the proportions were nearly equivalent in the intervention and control schools. The combined prevalence of overweight and obesity decreased in both the schools with the comprehensive intervention and the schools, in which only assessment was performed, although the comprehensive intervention was associated with greater improvements in indicators of adiposity, as well as, in blood insulin levels, among racially and ethnically diverse youth. These decreases may result in a reduction in the risk of type 2 diabetes.