Objective-To determine if there is a relationship between maternal perception of neighborhood safety in 3 rd grade and weight status in 5 th grade children, to test if gender moderates this relationship, and to identify potential mediators.Method-Data from 868 children and their mothers involved in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (NICHD-SECCYD) were used to examine the relationship between maternal perception of neighborhood safety in the 3 rd grade and child BMI z-score in the 5 th grade. Multiple regression models were used to test this relationship, the effect of gender, and potential mediating variables (time outdoors in neighborhood, television viewing, child behavior problems and puberty status).Results-Neighborhood safety ratings in the least safe tertile in 3 rd grade, compared to the safest tertile, were associated with an increased risk of obesity independent of gender, race and incometo-needs ratio (OR = 1.59; 95% CI 1.03, 2.46), and a higher child BMI z-scores in the 5 th grade among girls, but not boys, compared to the safest tertile (β = 0.33; 95% confidence interval, 0.09, 0.57). Neither amount of time spent outdoors in the neighborhood, television viewing, child behavior problems (internalizing or externalizing), nor puberty status altered the relationship.Conclusions-Maternal perception of the neighborhood as unsafe in 3 rd grade independently predicted a higher risk of obesity, and a higher BMI z-score among girls, but not boys, in the 5 th grade. The relationship was not explained by several potential mediators. Further investigation is needed to explore these gender differences and potential mediators.