During midlife years, women are at risk of increasing body weight and waist circumference. We evaluated changes in weight and waist circumference from enrollment to 2 years later and examined the influence of physical activity level on those changes among 232 women aged between 40 and 50. Weight increased significantly for the entire sample. Those who increased their physical activity from enrollment to 2 years later had the smallest increase in weight and had a slight decrease in waist circumference. To maintain ideal weight and waist circumference, midlife women should be encouraged to increase physical activity before and during the menopausal transition.