This 2-year prospective study examined the exercise and self-esteem model in middle-aged women (N = 143) previously enrolled in a randomized controlled exercise trial. Across the 2-year period, increases in physical activity (PA) and self-efficacy and reductions in body mass index (BMI) were associated with improved subdomain self-perceptions relative to physical condition, and reductions in BMI were associated with improved subdomain self-perceptions relative to physical condition and body attractiveness. The effects of PA, self-efficacy, and BMI on changes in physical self-worth and global self-esteem were mediated by changes in self-perceptions relative to physical condition and body attractiveness. The results of this longitudinal analysis support the hierarchical and multidimensional structure of self-esteem and indicate that middle-aged women can enhance how they perceive their condition and body attractiveness by continued participation in physical activity, increasing their self-efficacy, and maintaining healthy BMI levels.