Objective: Long-term psychological stress is associated with BMI increases in children as they transition to adulthood, whereas long-term maintenance of physical activity can slow excess weight gain.We hypothesized that in addition to these main effects, long-term physical activity mitigates the relationship between long-term stress and BMI increase.Method: The NHLBI Growth and Health Study enrolled 2,379 10-year-old Black and White girls, following them annually for 10 measurement points.Growth curve modeling captured the dynamics of BMI, measured yearly, and stress and physical activity, measured at varying years.Results: At average levels of activity and stress, with all covariates remaining fixed, average BMI at baseline was 19.74 (SE ϭ 0.38) and increased 0.64 BMI (SE ϭ 0.01, p Ͻ .001)units every year.However, this increase in BMI significantly varied as a function of cumulative stress and physical activity.Slower BMI gain occurred in those girls who were less stressed and more active (0.62 BMI units/year, SE ϭ .02,p Ͻ .001),whereas the most rapid and largest growth occurred in girls who were more stressed and less active (0.92 BMI units/year, SE ϭ .02,p Ͻ .001).Racial identification did not alter these effects.Conclusions: As hypothesized, in girls who maintained long-term activity, BMI growth was mitigated, even when reporting high long-term stress, compared with less physically active girls.This study adds to a converging literature in which physical activity, a modifiable prevention target, functions to potentially limit the damaging health effects of long-term psychological stress.