Irbesartan, an angiotensin-II inhibitor, has been shown to be an effective antihypertensive agent in clinical trials. The purpose of this study was to assess the cost-effectiveness of irbesartan in combination with hydrochlorothiazide (HCTZ) in Swedish health-care setting by predicting clinical events and life years based upon observed reductions in blood pressure in clinical trials. The cost-effectiveness of antihypertensive treatment with irbesartan compared with placebo and to other selected angiotensin-II inhibitors (losartan, valsartan, candesartan) in combination with HCTZ was estimated using a Markov model. The incidence of cardiovascular disease was obtained from the Swedish inpatient registry, whereas the risk reductions associated with antihypertensive therapy were taken from the medical literature. Costs for antihypertensive therapy and for treatment of cardiovascular events were included, and the health effects were measured in terms of quality-adjusted life years (QALYs). The study was conducted from a health-care payer perspective. For a 55-year-old male, irbesartan 150 mg/HCTZ 12.5 mg was a dominant strategy (better health effects at lower costs) when compared with losartan 50 mg/HCTZ 12.5 mg and valsartan 80 mg/HCTZ 12.5 mg, and the cost-effectiveness ratio compared with placebo was €3500 per QALY gained. In moderate-to-severe hypertension, irbesartan was cost-effective compared with losartan, whereas the results compared with candesartan were mixed. High-dose combination therapy of irbesartan was also found to be cost-effective compared with low-dose combination therapy. The results from the model indicate that irbesartan provides a cost-effective antihypertensive treatment strategy compared with both placebo, and to valsartan and losartan.