OBJECTIVES: Recently, the Flemish government has formulated several health objectives regarding healthy nutrition and physical exercise following recommendations from the WHO and the European Commission. The purpose of this study was to evaluate the cost-effectiveness of 16 potential health promoting interventions, related to these objectives. Interventions were aimed at the local community, the child environment, the workplace, health care providers and at information and communication channels. METHODS: A literature search was performed to determine the effectiveness of the interventions on short term intermediate outcome parameters and on diabetes and cardiovascular and oncologic events. Afterwards modeling was performed to predict the expected lifetime results in avoided DALY’s. The simulation was carried out on 4 age categories, i.e. 40, 50, 60 and 70-years old, assuming a 10-year implementation of the intervention. For the interventions aimed at children, a projection was made to later adult life, based on literature. In addition, the investments required for implementing the interventions during a 10-year period, and the costs of avoided events were calculated from a societal perspective. This allowed calculating the Return On Investment (ROI) and the full benefit cost ratio, assuming a value of €30,000 for avoiding one DALY. RESULTS: For the interventions aimed at the local community, the child environment, the workplace, health care providers and information and communication channels the average ROI equals to 9.59(1.32-22.44); 0.37(0.01-1.68); 1.98(0.56-4.52); 9.25(2.71-17.20); and 58.02(14.72-125.55) Euro per invested euro respectively. About half of the interventions have a positive ROI. The average full benefit cost ratio amounted to 36.36(5.89-71.36); 3.08(0.16-10.56); 9.14(3.33-20.04); 37.24(15.97-54.54); and 233.63(86.64-398.17) respectively. Only two interventions (aimed at the child environment) appeared not to be cost-beneficial for any age groups. CONCLUSIONS: Implementing interventions to promote a healthy lifestyle could generate a substantial amount of health gain leading to very beneficial benefit/cost ratios for a majority of interventions.