OBJECTIVES: Hypertension is an independent risk factor for cardiovascular disease, which results in an enormous burden to society, both in terms of health and costing. Therefore, health gains and related cost-savings could be achieved by optimizing antihypertensive treatment. The aim of this study was to estimate the cost-effectiveness of treating patients with hypertension in The Netherlands with angiotensin II receptor blockers (ARBs). METHODS: Our analysis comprised: 1) estimation of the cost-effectiveness based on a published, prospective, randomized, double-blind clinical trial comparing blood pressure lowering of olmesartan, losartan, valsartan and irbesartan; blood pressures at 8 weeks were inserted in the Framingham risk functions to estimate cardiovascular complications, using an international health economic model, and 2) a cost-minimization analysis (assuming comparable effectiveness) using daily practice prescription data from IADB.nl (50 pharmacies), a database covering a population of 500,000. RESULTS: After 8 weeks, the trial-based analysis showed that with olmesartan versus losartan, valsartan, and irbesartan a statistically significant larger decrease in blood pressure was achieved (11.5 versus 8.2, 7.9, and 9.9 mmHg [p<0.05], respectively). Furthermore, olmesartan resulted in most complications averted. Cost-effectiveness for olmesartan, losartan, valsartan, and irbesartan was estimated at €39,100, €77,100, €70,700, and €50,900 per cardiovascular complication averted, respectively. Pharmacy data showed that trial-dosing at 1 ‘Defined Daily Dose' (DDD) was not found in practice. On average, losartan, valsartan and irbesartan were consequently dosed above 1 DDD varying from 1.19 to 1.38 ‘Prescribed Daily Dose' (PDD), whereas olmesartan was dosed at 0.88 PDD and thus presenting (relatively) lower costs. CONCLUSION: Olmesartan was estimated to be the most cost-effective option of the four ARBs. However, due to differences found in within-trial versus daily practice dosing and absence of effectiveness data from daily practice, confirmation is needed from further prospective studies comparing ARBs based on comparable blood pressure control including hard endpoints.