Objective: Renal denervation (RDN) has been demonstrated to reduce muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in patients with resistant hypertension. Whether alterations of arterial stiffness may contribute to BP-lowering effects of RDN is unknown. Methods: We measured office BP and arterial stiffness using fingertip tonometry-derived augmentation index (EndoPAT2000) at baseline and at 3-month follow-up in 50 consecutive patients with resistant hypertension. Forty patients received RDN and 10 patients served as controls. MSNA was obtained in 20 RDN and 10 non-RDN patients. Results: Baseline BP averaged 170/92± 19/15 mmHg (RDN) and 171/93 ± 14/8 mmHg (non-RDN) despite the use of 4.9 ± 1.9 and 4.4±2.0 antihypertensive drugs, respectively. RDN significantly reduced SBP (170 ±19 vs. 154±25 mmHg; P< 0.001) and DBP (92 ±15 vs. 84±16mmHg; P<0.001), augmentation index (30.6 ± 23.8 vs. 22.7 ± 22.4%; P = 0.002), AI@75 corrected for heart rate (22.4±21.6 vs. 14.4±20.7; P = 0.002) and MSNA (80± 15 vs. 71 ± 18 bursts/100 heartbeats; P<0.01). Changes in AI@75 with RDN were unrelated to SBP (r= 0.043; P = 0.79), and DBP (r= 0.092; P = 0.57) and MSNA changes (r= - 0.17; P=0.49). No changes in BP, augmentation index, AI@75 or MSNA were observed in the non-RDN group. Conclusion: RDN results in a substantial and rapid reduction in augmentation index, which appears to be independent of BP and MSNA changes. These findings are indicative of a beneficial effect of RDN on arterial stiffness in patients with resistant hypertension and may contribute to the sustained BP-lowering effect of RDN.