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Aliskiren, a direct renin inhibitor, is effective for reducing blood pressure (BP) in patients with hypertension when combined with amlodipine or hydrochlorothiazide (HCTZ). However, the efficacy and tolerability of the 2 combinations are unclear. We performed a meta-analysis of randomized controlled trials of aliskiren/amlodpine and aliskiren/HCTZ for hypertension.The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and the Novartis clinical trial database were searched through December 2012 for reports of randomized controlled trials of aliskiren/amlodpine and aliskiren/HCTZ vs. monotherapy in patients with hypertension. The main outcome measures were reduction in systolic BP and diastolic BP from baseline and rates of therapeutic response and BP control. Tolerance of aliskiren/amlodipine and aliskiren/HCTZ was also analyzed. Outcomes were initially pooled by standard random-effects methods, producing a weighted mean difference (WMD) or risk ratio (RR) and 95% confidence intervals (CIs). The pooled estimates were then used for adjusted indirect comparisons.We selected 19 reports of trials involving 13,614 participants. Aliskiren/amlodpine and aliskiren/HCTZ were more effective than monotherapy in controlling BP. Aliskiren/amlodipine was significantly more effective than aliskiren/HCTZ in reducing systolic BP (WMD = −3.36mm Hg; 95% CI = −4.64 to 2.07mm Hg) and diastolic BP (WMD = −3.49mm Hg; 95% CI = −4.34 to 2.63mm Hg). As compared with aliskiren/HCTZ, alikiren/amlodipine was associated with higher rate of therapeutic response (RR = 1.23; 95% CI = 1.14–1.33) and BP control (RR = 1.24; 95% CI = 1.11–1.39). Number of adverse events and withdrawals due to adverse events were similar with aliskiren/amlodipine and aliskiren/HCTZ.BP control is better with aliskiren combined with amlodipine or HCTZ than with monotherapy, with aliskiren/amlodipine being more effective than aliskiren/HCTZ.