This study assessed the lifetime health and economic consequences of an efficacious scalable community weight loss program for overweight and obese adults. We applied a state-transition Markov model to project lifetime economic outcome (US dollar) and the degree of disease averted as a result of a weight loss intervention, compared with no intervention, from a payer perspective. Effect sizes of the intervention on weight loss, by sex, race and ethnicity, and body mass index (BMI) of participants, were derived from a 12-month community program. Relative risk of diseases across BMI levels and other parameters were informed by the literature. A return on investment (ROI) analysis was conducted to present the overall cost-benefit of the program. Simulation results showed that among 33,656 participants and at a cost of $2.88 million, the program was predicted to avert (with a corresponding estimated medical costs saved of) 78 cases of coronary heart disease ($28 million), 9 cases of strokes ($971,832), 92 cases of type 2 diabetes ($24 million), 1 case of colorectal cancer ($357,022), and 3 cases of breast cancer ($483,259) over the participant lifetime. The estimated medical costs saved per participant was $1,403 ($1,077 of African American men and $1,532 of Hispanic men), and the ROI was $16.7 ($12.8 for African American men and $18.3 for Hispanic men) for every $1 invested. We concluded that a scalable efficacious community weight loss program provides a cost-effective approach with significant ROI, which will assist informed decisions for future adoption and dissemination.