The efficacy and safety of an olmesartan medoxomil (OM)–based treatment algorithm was tested in a double-blind, randomized, placebo-controlled titration study in 276 patients with stage 1 or 2 hypertension. After placebo run-in, patients were randomized to placebo (12 weeks) or OM 20 mg/d (weeks 1–3). OM was up-titrated to 40 mg/d (weeks 4–6), then OM/hydrochlorothiazide (HCTZ) 40/12.5 mg/d (weeks 7–9) and OM/HCTZ 40/25 mg/d (weeks 10–12) were started if blood pressure (BP) remained ≥120/80 mm Hg at each time interval. End points were change from baseline in mean systolic BP (primary) and mean diastolic BP (secondary). OM-based treatment was well tolerated and changed BP by −22.3/−12.1 mm Hg from baseline vs −0.1/+0.8 mm Hg for placebo (P<.0001). Cumulative goal BP (<140/90 mm Hg) was achieved in 74.1% and 30.7% of OM- compared with placebo-treated patients, respectively (P<.0001). BP normalized (<120/80 mm Hg) in 44.8% of OM- vs 1.4% of placebo-treated patients with stage 1 hypertension (P<.0001).