OBJECTIVES: According to current Dutch guidelines, antihypertensive treatment for patients with mild hypertension is recommended if the 10-year fatal cardiovascular disease (CVD) risk exceeds 10% or if accompanying risk factors are present. Recent evidence suggests that lifelong CVD risk estimates might be more informative than 10-year risk estimates. The aim of this study was to estimate the economic impact and influence on CVD risk of blood pressure (BP) reduction, in patients ineligible for treatment according to guidelines. METHODS: A Markov model was developed to assess the lifetime costs and health benefits of BP reduction with hydrochlorothiazide (HCT) or HCT plus losartan. Patients had mild hypertension and low 10-year CVD risk. The SCORE risk estimates were modified to predict fatal and non-fatal events over a lifelong time horizon. We analysed scenarios for different age groups, gender and reductions in BP. Costs and health effects were discounted at 4.0% and 1.5%, respectively; a Dutch healthcare perspective was used. RESULTS: A total of 48 different scenarios were modeled. Minor BP reductions were potentially not cost-effective in young women treated with HCT (€59,000 per life-year gained (LYG)), whereas potential cost-effectiveness was observed in a comparable male population (€12,000 per LYG). BP reduction was, generally, found to be more cost-effective in men, in older subjects and for larger BP reductions (up to cost-saving results). Results for HCT plus losartan were comparable. CONCLUSIONS: In patients ineligible for antihypertensive treatment according to current Dutch guidelines, reducing BP, nonetheless, resulted in clinical benefits for several patient populations. BP reduction was found to be potentially cost-effective in males for all age groups and even cost-saving in older ages, whereas for females it was less favorable. This, together with recent decreases in drug prices, should trigger further discussion on antihypertensive treatment in patients with low 10-year fatal CVD risk.