Background/Aims: Only 45% of adults get the recommended level physical activity (PA), and adolescents are similarly inactive. Insufficient PA is a major contributing factor to obesity and disease risk. The Guide to Community Preventive Services (Community Guide) published by the Task Force on Community Preventive Services recommends several physical activity interventions in community settings. However, the Community Guide does not indicate which interventions provide the biggest reach and impact given a community’s size and demographic profile. This study assessed the health and medical cost impacts of several Community Guide recommended community-based, populationwide interventions across different settings. Methods: We developed a physical activity microsimulation model (PAMM) to track lifetime physical activity (PA) and body mass index (BMI) based upon an individual’s age, gender, education, and income level. The PAMM translates the intermediate outcomes of PA and BMI into cardiovascular burden (coronary) heart disease, stroke, and diabetes). The PAMM was used to estimate the health (Quality Adjusted Life Years [QALYs]) and medical cost impact of five recommended interventions upon two representative cross-sections: one from a large (pop>100k), the other from a small (pop<50k) urban environment. The interventions were: Enhanced School-Based Physical Education, Point-of-Decision (POD) Prompts, The Creation of Places for Physical Activity with Informational Outreach, Street-Scale Urban Design and Land Use, Community-Wide Campaigns, and Social Support Interventions. Results: Results are in terms of 100,000 persons. Among children, structured curriculum changes had the largest impact with a 29.9% increase recommended PA level achievement and a 2% decrease in lifetime obesity (BMI>30). Among adults, results differed by setting. In large urban areas, POD prompts were most effective (3.2% increase in PA adherence and 6,607 QALYs saved). In small urban areas, Community-Wide Campaigns were most effective (1.1% increase in PA adherence 5,753 QALYs saved). Community-Based Social Support was found least effective in both settings. Conclusion: All of the evaluated interventions appeared to increase physical activity and reduce medical utilization. However, effectiveness varied by setting and population, and detailed modeling can help policy-makers identify optimal strategies.