In a multicenter, randomized, double-blind trial, the authors compared the antihypertensive efficacy of once-daily treatment with the new angiotensin II type 1 receptor blocker (ARB) olmesartan (20 mg) with recommended starting doses of losartan (50 mg), valsartan (80 mg), and irbesartan (150 mg) in 588 patients with a cuff diastolic blood pressure (DBP) of ≥100 and ≥115 mm Hg and a mean daytime DBP of ≥90 mm Hg and <120 mm Hg, as measured by ambulatory blood pressure monitoring. Cuff and ambulatory blood pressures were monitored at baseline and after 8 weeks of treatment. All groups were predominantly white and approximately 62% male, and their mean age was approximately 52 years. In all groups, mean baseline DBP and systolic blood pressure (SBP) were approximately 104 and 157 mm Hg, respectively. The reduction of sitting cuff DBP with olmesartan (11.5 mm Hg), the primary efficacy variable of this study, was significantly greater than with losartan, valsartan, and irbesartan (8.2, 7.9, and 9.9 mm Hg, respectively). Reductions of cuff SBP with the four ARBs ranged from 8.4–11.3 mm Hg and were not significantly different. The reduction in mean 24-hour DBP with olmesartan (8.5 mm Hg) was significantly greater than reductions with losartan and valsartan (6.2 and 5.6 mm Hg, respectively) and showed a trend toward significance when compared to the reduction in DBP with irbesartan (7.4 mm Hg; p=0.087). The reduction in mean 24-hour SBP with olmesartan (12.5 mm Hg) was significantly greater than the reductions with losartan and valsartan (9.0 and 8.1 mm Hg, respectively) and equivalent to the reduction with irbesartan (11.3 mm Hg). All drugs were well tolerated. The authors conclude that olmesartan, at its starting dose, is more effective than the starting doses of the other ARBs tested in reducing cuff DBP in patients with essential hypertension.