Objectives: Antihypertensive therapy is effective to control blood pressure (BP) and to prevent cardiovascular events, but the further treatment strategies for patients who cannot achieve goal BP with low-dose monotherapy is still under dispute. Our study investigates the effects of high-dose amlodipine and valsartan and their low-dose combination on blood pressure variability (BPV) and pulse wave velocity (PWV) to provide references for clinical medication. Materials and Methods: This study was a prospective, randomized, parallel, case-controlled trial performed in a medical center. A total of 134 outpatients newly diagnosed with essential hypertension or receiving low-dose monotherapy were enrolled and 119 completed the trial. They were randomized into amlodipine 10 mg group (n = 40), valsartan 160 mg group (n = 38) and amlodipine 5 mg + valsartan 80 mg (n = 41) in a 1:1:1 allocation ratio for a 10-week treatment. Demographic data and laboratory indicators were collected at the randomization and 10 weeks after the treatment. The 24-hour ambulatory BP and brachial-ankle PWV were also monitored. Results: All therapies reduced systolic and diastolic BP (P < 0.05). The 24-hour systolic BPV was significantly decreased in amlodipine and combination groups (3.55 +/- 2.57, 4.11 +/- 2.20 versus 2.23 +/- 2.54 mm Hg, P < 0.05). The effects on diastolic BPV differed between different treatments. PWV was lowered by 3 antihypertensive schemes; the degree of which from strongest to weakest were valsartan, combination and amlodipine (228.87 +/- 60.41 versus 152.49 +/- 49.25 versus 99.35 +/- 35.57 cm/second, P < 0.01). Conclusions: All further strategies can effectively control BP. The combination treatment reduces both BPV and PWV noticeably, whereas double-dose amlodipine achieves the greatest BPV decrease and valsartan is best in controlling PWV.