This study assessed blood pressure (BP) reductions and response rates following addition of nebivolol to ongoing antihypertensive therapy in patients with uncontrolled stage I-II hypertension despite antihypertensive treatment. Patients with an average sitting diastolic BP (SiDBP) > or =90 and < or =109 mm Hg while taking an antihypertensive regimen were included in this double-blind, placebo-controlled, parallel-group study. The primary efficacy end point was reduction from baseline to week 12 in mean trough SiDBP. In total, 669 patients were randomized to once-daily nebivolol 5, 10 or 20 mg or placebo. Addition of nebivolol 5, 10 and 20 mg significantly reduced BP; placebo-subtracted least squares mean reductions in trough SiDBP were -3.3, -3.5 and -4.6 mm Hg, respectively (P<0.001) and -5.7, -3.7 and -6.2 mm Hg in trough sitting systolic BP (SiSBP), respectively (P< or =0.015). Adding nebivolol 5-20 mg resulted in significantly more responders (SiDBP <90 or > or =10 mm Hg reduction; range: 53.0-65.1 vs 41.3% with placebo; P< or =0.028) and significantly better control rates (SiSBP/SiDBP <140/90 mm Hg; range: 41.3-52.7 vs 29.3% with placebo; P< or =0.029). Nebivolol was well tolerated; the incidence of adverse events with nebivolol was similar to that with placebo (40.2 vs 38.9%, respectively; P=0.763). Addition of once-daily nebivolol to ongoing antihypertensive therapy provided significant additional BP reductions and better response rates in patients with uncontrolled hypertension and was well tolerated.