In this multicenter trial, the effects of nebivolol added to an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) were assessed in patients with hypertension (diastolic blood pressure [DBP] 80–110 mm Hg) and prediabetes (fasting blood glucose 100–125 mg/dL and/or 2-hour oral glucose tolerance test [OGTT] 140–199 mg/dL). After a 4-week run-in period (in which lisinopril [10 mg/d] or losartan [50 mg/d] treatment was initiated), patients with DBP 90–110 mm Hg were randomized (2:2:1) to 12-week, double-blind treatment with nebivolol (n=223; 5–40 mg/d), hydrochlorothiazide (HCTZ; n=212; 12.5–25 mg/d), or placebo (n=102), titrated to achievement of 130/80 mm Hg. The primary outcome measure was DBP (last observation carried forward, intent to treat population); secondary measures included systolic blood pressure (SBP) and glucose levels. At baseline, overall mean values for body mass index, triglycerides, and high-density lipoprotein cholesterol were 32.3 kg/m2, 1.7 mmol/L, and 1.3 mmol/L, respectively. At week 12, nebivolol and placebo groups demonstrated a decrease of −9.4 and −5.0 mm Hg, respectively (P<.001) for DBP and −10.4 and −7.8 mm Hg for SBP (P=.147). The mean changes in area under the curve OGTT were 0.0 mg/dL (nebivolol), 6.9 mg/dL (HCTZ; P=.024 vs nebivolol), and −1.0 mg/dL (placebo). Adverse event–related discontinuation rates were 10.3%, 6.6%, and 2.0%, respectively. Nebivolol, added to an ACE inhibitor or ARB, provides additional blood pressure reduction with little or no effect on glucose metabolism in hypertensive patients with prediabetes.