Background: Physical activity is assumed to reduce excessive fatness in children. This study examined whether the benefits of early childhood moderate-to-vigorous physical activity (MVPA) on fatness are sustained throughout childhood. Methods: MVPA minutes per day (min/d) and fat mass (kilograms; kg) were measured using accelerometry and dual-energy x-ray absorptiometry in 333 children aged 5, 8, and 11 years who were participating in the Iowa Bone Development Study. Mixed regression models were used to test whether MVPA at age 5 years had an effect on fat mass at age 8 years and age 11 years, after adjustment for concurrent height, weight, age, maturity, and MVPA. The analysis was repeated to control for fat mass at age 5 years. Using mixed-model least-squares means, adjusted means of fat mass at age 8 years and age 11 years were compared between the highest and lowest quartiles of MVPA at age 5 years. Data were collected between 1998 and 2006 and analyzed in 2008. Results: For boys and girls, MVPA at age 5 years was a predictor of adjusted fat mass at age 8 years and age 11 years (p<0.05). In girls, the effect of MVPA at age 5 years was not significant when fat mass at age 5 years was included. Boys and girls in the highest quartile of MVPA at age 5 years had a lower fat mass at age 8 years and age 11 years than children in the lowest MVPA quartile at age 5 years (p<0.05; mean difference 0.85 kg at age 8 years and 1.55 kg at age 11 years). Conclusions: Some effects of early-childhood MVPA on fatness appear to persist throughout childhood. Results indicate the potential importance of increasing MVPA in young children as a strategy to reduce later fat gains.