Objective: The aim of this study was to examine the individual and combined associations of leisure-time physical activity and sleep with cardiovascular risk factors in postmenopausal women. Methods: We analyzed 48-month cross-sectional follow-up data from 393 participants of the Women on the Move Through Activity and Nutrition Study, a behavioral weight loss trial. Leisure-time physical activity data were collected with the past-year Modifiable Activity Questionnaire, whereas sleep data were collected with the Pittsburgh Sleep Quality Index. We compared physical activity and sleep categories using analysis of variance, post hoc Scheffe tests, and multivariate analyses based on groups above/below the median leisure-time physical activity level, above/below the sleep quality value of 5, and above/below the sleep duration of 7 hours/day. Results: The average sleep quality and sleep duration did not significantly differ between women with high and women with low physical activity levels. When women with good sleep quality were compared, higher physical activity levels were associated with lower body mass index (2.0 kg/m 2; 25, 75 quartiles, 0.3, 3.6), waist circumference (6.3 cm; 1.7, 10.9), and total body fat (2.1%; 0.3, 4.0; P < 0.05). When participants with poor sleep quality were compared, highly active women had lower trunk fat, total body fat, and insulin levels than less active women did (P < 0.05). In multivariate analysis, physical activity was significantly associated with high-density lipoprotein level, trunk fat, and total body fat after controlling for sleep quality, sleep duration, age, hormone therapy and smoking status, and body mass index. Conclusions: The combined associations of leisure-time physical activity and sleep suggest that cardiovascular risk factors are more favorable in highly active women relative to less active women regardless of sleep. © 2012 by The North American Menopause Society.