Arterial stiffness and wave reflection are independent predictors of cardiovascular events. This study compared the effect on arterial stiffness and wave reflection of a combination therapy with an ACE-inhibitor plus calcium channel blocker or thiazide diuretic in essential hypertensive patients with metabolic syndrome uncontrolled by ACE-inhibitor monotherapy. In a multicenter randomized, open, parallel group study, 76 hypertensive patients with metabolic syndrome, after 4 weeks run-in with Enalapril 20 mg, were randomized to a combination therapy with Lercanidipine (LER, 10-20 mg) or Hydrochlorothiazide (HCT, 12,5-25 mg) for 6 months. Applanation tonometry was used to measure aortic stiffness (carotid to femoral pulse wave velocity, PWV), central blood pressure (BP) and augmentation index (AI), a marker of wave reflection. At screening, office BP was 153±4/95±2 mmHg in both groups. After run in, BP was 139±18/84±12 and 142±17/84±10 mmHg, in the LER and HCT groups, respectively, and after 6-month it was 134±15/79±9 mmHg in the LER group and 134±14/79±10 mmHg in the HCT group. No significant difference between the two groups was observed. Central BP values had a similar behavior (6 months: LER 120±13/80±9 mmHg; HCT 122±13/79±9 mmHg). PWV was similar at baseline and was equally reduced by the two treatments (LER from 8.6±1.5 to 8.1±1.3 m/s; HCT from 8.5±1.2 to 8.2±1.0 m/s). Finally, both drugs reduced AI, but this reduction resulted significantly greater in LER than in HCT arm (LER from 26.8±10.9 to 20.6±9.1%; HCT from 28.2±9.0 to 24.7±8.7%). In conclusion, the addition of LER caused the same PWV reduction as compared to HCT but greater reduction in AI in hypertensive patients with metabolic syndrome not controlled with Enalapril alone. These results indicate a positive effect of the combination with LER on wave reflection, suggesting a potential role for cardiovascular protection.