BACKGROUND Catheter-based renal denervation (RDN) reduces local and whole-body sympathetic activity and blood pressure (BP) in patients with resistant hypertension. However, safety concerns exist concerning the development of orthostatic dysfunction after RDN. RESULTS In 36 patients (65 ± 7.6 years, 75% male) with resistant hypertension (office BP 162 ± 24/91 ± 14 mm Hg) treated with 4.8 ± 1.7 antihypertensive drugs, tilt table testing (TTT) was performed before and three months after RDN. Response to RDN was defined as a reduction in office systolic BP (SBP) ≥ 10 mm Hg three months after RDN. Responders (n=26; 72.2%) and non-responders (n=10; 27.8%) were evaluated separately. After RDN, office SBP and diastolic BP (DBP) were reduced by 29 ± 6.2/14 ± 3.6 mm Hg (p<0.0001; p=0.0002) only in responders. During TTT, SBP and DBP in supine position were only reduced in responders. Resting heart rate (HR) decreased in responders but not in non-responders by 5.9 ± 1.7beats/min (p=0.0016). Mean and minimal SBP were not altered during passive tilting. In the responder group, ∆SBP was reduced in the initial phase of tilting. The adaptive increase of HR was preserved in both groups after RDN, while only in responders mean and minimal HR were reduced after passive tilting. Following drug provocation, mean and minimal SBP during all phases of passive tilting remained unchanged. ∆SBP, ∆HR and total number of (pre-)syncopes were neither influenced by RDN nor differing between responders and non-responders. CONCLUSIONS In patients with resistant hypertension, RDN reduced office BP, supine BP and HR during TTT without causing orthostatic dysfunction or (pre-)syncopes three months after treatment.