Background and Objectives: With prevalence of childhood obesity increasing rapidly, developing of effective and sustainable intervention strategies is becoming more and more important for the prevention of childhood obe- sity in China. A trial was developed to evaluate the effect of comprehensive school-based intervention on child- hood obesity. Methods and Study Design: A multi-center cluster randomized controlled trial was conducted among urban children (n=9,867) aged 6-13 years in 38 primary schools from six large cities. Comprehensive in- tervention, nutrition education and physical activity interventions were carried out among children. Nutrition ed- ucation was also targeted towards teachers, parents and health workers in intervention schools. The program was implemented for 2 semesters from May 2009 to May 2010. Results: The combined prevalence of overweight and obesity increased by 1.5 percent (22.7% vs 24.2%, p<0.001) in control group while 0.2 percent in comprehensive intervention group (23.6% vs 23.8%, p=0.954) after intervention (p=0.067). The effect was significantly stronger among girls than boys (-1.4% vs -0.9%, p=0.028). A significant intervention effect was found on BMI for -0.3 kg/m2 (95% confidence interval (CI): -0.4, -0.2; p<0.001), BMI z scores for -0.14 (95% CI: -0.18, -0.11; p<0.001)，body fat for -0.8 percent (95% CI: -0.9, -0.6; p<0.001), waist circumference for -0.5 cm (95% CI: -0.6, -0.3; p<0.001), blood serum glucose for -0.20 mmol/L (95% CI: -0.24, -0.16; p<0.001) and cholesterol for -0.32 mmol/L (95% CI: -0.34, -0.30; p<0.001). Conclusions: We observed moderately significant effects on combined prevalence of overweight and obesity, BMI, BMI z scores, waist circumference, percentage body fat, glucose and lipid for a comprehensive school-based intervention of childhood obesity in China.