INTRODUCTION: Patients with stage 2 hypertension require large absolute reductions in blood pressure (BP) to achieve recommended BP goals. Combination therapy with the direct renin inhibitor, aliskiren, and the angiotensin receptor blocker, valsartan, has been shown to produce greater BP reductions than either agent alone in a double-blind study in 1797 hypertensive patients. METHODS: This post-hoc analysis evaluated the BP-lowering efficacy of aliskiren in combination with valsartan in a subset of patients (n=581) with stage 2 hypertension (baseline mean sitting systolic BP [msSBP] > or =160 mmHg). Patients were randomized to receive aliskiren/valsartan 150/160 mg, aliskiren 150 mg, valsartan 160 mg, or placebo once daily for 4 weeks followed by 4 weeks at double the initial dose. Mean changes from baseline in msSBP and mean sitting diastolic BP were assessed at week-8 endpoint (intent-to-treat population). RESULTS: Aliskiren/valsartan 300/320 mg reduced BP from baseline by 22.5/11.4 mmHg at week-8 endpoint. BP reductions with combination therapy were significantly greater than with aliskiren 300 mg (17.3/8.9 mmHg, P<0.05), valsartan 320 mg (15.5/8.3 mmHg, P<0.01), or with placebo (7.9/3.7 mmHg, P<0.0001). BP control rates (<140/90 mmHg) were also significantly higher (P<0.05) with aliskiren/valsartan 300/320 mg (29.8%) compared with either aliskiren 300 mg (19.0%) or valsartan 320 mg (13.8%) monotherapy, or placebo (8.9%). All treatments were generally well tolerated. CONCLUSION: Combination therapy with aliskiren and valsartan provided significantly greater BP reductions over aliskiren or valsartan monotherapy and is an appropriate option for management of BP in patients with stage 2 hypertension.