Background: Although walking is the most popular leisure-time activity for adults, few long-term, longitudinal studies have examined the association between walking, an affordable and accessible form of physical activity, and weight gain. Objective: The objective was to evaluate the association between changes in leisure-time walking and weight gain over a 15-y period. Design: Prospective data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study of 4995 men and women aged 18-30 y at baseline (1985-1986) from 4 US cities and reexamined 2, 5, 7, 10, and 15 y later. Sex-stratified, repeated-measures, conditional regression modeling with data from all 6 examination periods (n = 23,633 observations) was used to examine associations between walking and annualized 15-y weight change, with control for 15-y nonwalking physical activity, baseline weight (and their interaction), marital status, education, smoking, calorie intake, and baseline age, race, and field center. Results: Mean (±SE) baseline weights were 77.0 ± 0.3 kg (men) and 66.2 ± 0.3 kg (women), weight gain was ≈1 kg/y, and the mean duration of walking at baseline was <15 min/d. After accounting for nonwalking physical activity, calorie intake, and other covariates, we found a substantial association between walking and annualized weight change; the greatest association was for those with a larger baseline weight. For example, for women at the 75th percentile of baseline weight, 0.5 h of walking/d was associated with 8 kg less weight gain over 15 y compared with women with no leisure time walking. Conclusion: Walking throughout adulthood may attenuate the long-term weight gain that occurs in most adults. © 2009 American Society for Nutrition.