J Clin Hypertens (Greenwich) . 2011;13:571–581. ©2011 Wiley Periodicals, Inc. Initial multiple drug therapy for hypertension achieves greater and quicker reductions and higher blood pressure (BP) control rates than monotherapy. This 8‐week, prospective, multicenter, randomized, double‐blind study compared the efficacy and safety of the initial combination of aliskiren/amlodipine with amlodipine monotherapy in African Americans with stage 2 hypertension. After a 1‐ to 4‐week washout, patients received aliskiren/amlodipine 150/5 mg or amlodipine 5 mg for 1 week and then were force‐titrated to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg for 7 weeks. At week 8, greater reductions in mean sitting systolic BP were obtained with aliskiren/amlodipine (n=220) than with amlodipine (n=223) (least squares mean change [standard error of the mean], −34.1 [1.14] mm Hg vs −28.9 [1.12] mm Hg; P <.001). Ambulatory and central BP measures were consistent with clinic BP findings, although these were conducted in a small subset of patients (n=94 in ambulatory BP monitoring substudy and n=136 for central BP). More patients achieved goal BP (<140/90 mm Hg) with aliskiren/amlodipine than with amlodipine at week 8 (57.3% vs 48.0%; P = .051). Both treatment groups had similar adverse event rates (35.0% and 32.7%, respectively). The most common adverse events were peripheral edema (7.7% with aliskiren/amlodipine and 9.0% with amlodipine), headache, fatigue, and nausea. The combination of aliskiren/amlodipine reduced peripheral, ambulatory, and central BP more than amlodipine alone with similar tolerability in African Americans with stage 2 hypertension.