Background/Purpose Catheter-based renal sympathetic denervation (RDN) can reduce blood pressure (BP) and sympathetic activity in certain patients with uncontrolled hypertension. Less is known about the impact of renal anatomy and procedural parameters on subsequent BP response. Methods/Materials A total of 564 patients with resistant hypertension underwent bilateral RDN in 9 centers in Europe and Australia using a mono-electrode radiofrequency catheter (Symplicity Flex, Medtronic). Anatomical criteria such as prevalence of accessory renal arteries (ARA), presence of renal artery disease (RAD), length, and diameter were analyzed blinded to patient's characteristics. Results ARA was present in 171 patients (30%), and RAD was documented in 71 patients (13%). On average 11 ± 2.7 complete 120-s ablations were performed, equally distributed on both sides. After 6 months, BP was reduced by 19/8 mmHg (p < 0.001 for both). Change of systolic blood pressure (SBP) was not related to the presence of ARA (−18 vs. −20 mmHg; p = NS) or RAD (−16 vs. −20 mmHg; p = NS). Patients with a bilateral diameter ≤4 mm had a more pronounced reduction of SBP compared to patients with a unilateral diameter ≤4 mm or a bilateral diameter >4 mm (−29 vs. −26 vs. −17 mmHg; p < 0.001). Neither the length of the renal artery nor the number of RF ablations influenced BP reduction after 6 months. Conclusions The diameter of renal arteries correlated with SBP change after RDN at 6-month follow-up. Change of SBP was not related to the lengths of the renal artery, presence of ARA, RAD, or the number of RF ablations delivered by a mono-electrode catheter.