Copyright © 2016 Wolters Kluwer Health, Inc.Objectives: Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with hypertension. The effects on resting and ambulatory heart rate (HR), also regulated by the sympathetic nervous system, are not established. Methods: Herein, we report 12-month outcomes from the Global SYMPLICITY Registry on office and ambulatory HR and BP in patients with uncontrolled hypertension (n=846). Results: HR declined in correlation with the HR at baseline and at 12 months, in particular, in patients in the upper tertile of HR (>74 bpm). BP reduction was similar in the tertiles of HR at baseline. Similar effects were observed when 24-h ambulatory HR and SBP were determined. Office HR was similarly decreased when patients were on a b-blocker or not. Antihypertensive treatment remained unchanged during the 12-month period of the Global SYMPLICITY Registry. Conclusion: RDN reduces BP independent from HR. A HR reduction is dependent on baseline HR and unchanged by b-blocker treatment. The effects of RDN on SBP and HR are durable up to 1 year. HR reduction might be a target for RDN in patients with high HR at baseline, which needs to be scrutinized in prospective trials.