OBJECTIVES To evaluate the incremental cost-effectiveness of four angiotensin receptor blockers in hypertension, in a large US managed care setting. METHODS A decision analytical model was developed to estimate costs to reach JNC-7 blood pressure (BP) goal for four ARBs: olmesartan (OLM), valsartan (VAL), irbesartan (IRB), and losartan (LOS). The study period was 5/1/01 to 12/31/06. Patients were ≥18 years, have ≥2 claims for the Index ARB, a medical claim for HTN (ICD-9 codes 401.xx-404.xx), and minimum 6 months pre- and 9 months post-index eligibility. Outcomes were all-cause and HTN-attributable actual plan costs to achieve JNC 7 goal (<140/90, <130/80 with diabetes mellitus, DM). Costs were calculated for over 120,000 eligible patients receiving ARBs in the plan. BP goal attainment was determined from 1293 medical charts and linked to costs in the claims database. Model robustness was tested using Monte Carlo simulation and probabilistic sensitivity analysis (PSA). RESULTS 121,472 patients met inclusion criteria. Mean age was 55.2 years, 22 % had DM. ARB cohorts were (n) OLM (19,525); VAL (59,176); IRB (17,226) and LOS (25,546). OLM was found more effective in achieving JNC 7 goal, and to incur lower all-cause and HTN-attributable costs, dominating other options. The CE ratios per percent of patients to reach HTN goal for OLM were $8,964 (all-cause costs) and $2,704 (HTN-attributable costs), compared to the ratios for LOS ($10,848 and $3,291), VAL ($10,557 and $3,577) and IRB ($13,397 and $4325). (All costs adjusted to 2006 CPI). Monte Carlo and PSA results were consistent with the baseline analysis. CONCLUSIONS Compared to VAL, IRB and LOS, OLM was found to be the most cost-effective of the four ARBs for the treatment of hypertension in a large US managed care population.