Objective:The objective of this study was to evaluate the effects of a multilevel healthy lifestyle behavior change program for women living in rural areas where higher rates of cardiovascular disease are influenced by poverty, reduced access to health care and unique social and built environment challenges.Methods:In eleven medically underserved rural towns in New York, 182 overweight and obese sedentary women 40 years and older enrolled in a community-randomized trial. Communities randomized to Group 1 (intervention) participated in six months of hour-long, twice weekly experiential learning classes that included progressive strength training, aerobic exercise and skill-based nutrition education (individual level), and a civic engagement curriculum focused on healthy food and physical activity environments (social, community and policy levels); classes were facilitated by local health educators trained by the research team. Communities randomized to Group 2 (delayed intervention control) received the intervention immediately following the completion of intervention activities for Group 1. All components of the Simple 7 score were recorded at baseline (prior to randomization) and at six months (post-intervention for Group 1, pre-intervention for Group 2). Weight, height, blood pressure, blood cholesterol and blood glucose were measured directly and smoking status, diet and physical activity were self-reported. Multivariate regression analyses were used to examine change in Simple 7 score from baseline to outcome. Initial models controlled for study site, baseline Simple 7 score, education and age, and were based on the 107 participants with complete data.Results:Simple 7 scores were similar for both groups prior to randomization (7.91 for Group 1, 7.83 for Group 2). At the end of the six month intervention period for Group 1, the Simple 7 score for Group 2 was unchanged (7.85) but increased to 8.98 for Group 1 participants (p=0.02 for the difference between groups in Simple 7 change). The percentage of Group 1 participants in the optimal range of scores (10-14) rose from 14.8% to 37.0%. The Simple 7 components showing the greatest improvement were BMI, physical activity and healthy diet score. Additional analyses will assess potential bias associated with incomplete data and will examine evidence for the validity of self-reports on physical activity and diet.Conclusion:The multilevel healthy lifestyle program is feasible for implementation in rural settings with limited resources and showed promise for reducing cardiovascular disease risk in midlife and older rural overweight and obese women.