OBJECTIVES: To describe how Thailand use evidence on country’s burden of disease and cost-effectiveness of health interventions from the 2nd edition Disease Control Priority in Developing Countries (DCP2) to set priorities in health sector investment in the National Health Development Plan. METHODS: The study applies comprehensive literature reviews, secondary data analyses, interview of key informants and meeting among stakeholders to answer four specific objectives: a) burden of disease (BOD) priorities; b) health interventions currently implemented in Thailand against what recommended by DCP2; c) costs of top-ten BOD in terms of medical expenditure, productivity loss due to life loss and morbidity; and d) assessment of medium term economic framework in different scenario.  RESULTS: Since 1999 there has been an increasing trend in BOD attributable from alcohol and tobacco consumption, consumption of high fat high calorie diet, lack of fibre food and physical activities, increasing incidence of diabetes mellitus, hypertension and high blood lipid, traffic injuries, overweight and obesity.  Evidence from the share of DALY loss, productivity loss and absenteeism from morbidity indicates three national health priorities: HIV/AIDS; traffic injuries and diabetes mellitus.  Total health expenditure in 2009 was 179 USD per capita, 4.3% of GDP, and mostly spent on curative services, only 4.5% of that was for disease prevention and health promotion.  CONCLUSIONS: Thailand can invest more on health of the population, in particular on disease prevention and health promotion to address three national health priorities: HIV/AIDS, traffic injuries and diabetes mellitus through cost effective interventions in and outside the health sector. The most probable scenario for increasing investment in health promotion and disease prevention is to double the amount of investment for health promotion and disease prevention.  Also, resources can be mobilized from local administrations and communities, and should be managed by efficient and accountable agency with effective mechanisms.