Background: Childhood obesity and overweight have become major public health problems worldwide. To combat this problem, effective, sustainable, and consistent strategies are needed. In this study, the long-term effect of a school-based intervention for weight reduction was evaluated in primary school students in Tehran, Iran. Methods: This was a cluster randomized controlled trial (RCT) conducted in 12 primary schools in a low- to middle-class district in Tehran, Iran. The participants were 334 overweight or obese primary school students (girls =164) based on World Health Organization standards, equally distributed in the intervention (n=167) and comparison (n=167) groups. It was a multi-component intervention and included nutrition education and increased physical activity (PA), a lifestyle modification program for parents, and changing the food items sold in canteens of the schools. Body mass index Z-score [BMI-Z] was determined as the primary outcome and measured at baseline, three months after baseline, at post-test (after 18 weeks), and follow-up (13-month). In total, 205 students (59.5%) completed the follow-up. Analyses were carried out based on the intention-to-treat principle using linear mixed models. Results: After 13 months, the BMI Z-score decreased in both intervention and comparison groups. However, the change was more significantly observed in the intervention group (adjusted change: 0.098, 95% CI: (0.03-0.16) compared with comparison group (P=0.003(. The intervention had a more significant effect on BMI Z-score among girls (adjusted change: 0.36, 95% CI: (0.27-0.45) compared with the comparison group (P<0.001)( than among boys (adjusted change: -0.14, 95% CI: (-0.23- -0.05) compared with the comparison group (P=0.002). Conclusion: The intervention was an effective way to reduce BMI in the girls and the effect lasted for a relatively long time.