OBJECTIVES: : To assess cost-effectiveness of blood pressure and/or cholesterol lowering drugs for cardiovascular disease prevention. METHODS: Design: A Markov model using Generalized Cost-Effectiveness Analysis with ‘do-nothing’ as a comparator; health sector perspective on life time cost-effectiveness and 3% discounting for both cost and effects. Setting: Primary care, Thailand Target Population: Thai population aged 30 years or above in 2004 classified by 10-year absolute risk of cardiovascular disease. Intervention: Blood pressure and cholesterol lowering drugs. Outcome Measure: Average and incremental cost-effectiveness in Thai baht per disability adjusted life year averted. RESULTS: Base-Case Analysis: The most cost-effective option for cardiovascular disease prevention in people with 10-year risks of 5% and greater was the polypill followed by combinations of three blood pressure drugs with or without a statin. Single generic drugs, except angiotensin reuptake blockers  were also very cost-effective, but dominated by drug combinations due to greater health gain and shared costs.  Sensitivity Analysis: All generic drugs except beta blockers and angiotensin reuptake blockers, and the above combinations were very cost-effective; the median cost effectiveness ratios for all of these drugs were below one times gross domestic product per capita  in people with 10-year risks of 5% and greater. CONCLUSIONS: : Primary cardiovascular disease prevention with a combination of generic drugs in Thailand is very cost-effective when the 10 year absolute risk is 5% or higher.