The Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study of the safety and effectiveness of renal denervation in subjects with uncontrolled hypertension. Bilateral renal denervation will be performed using the Symplicity Catheter - a percutaneous system that delivers radiofrequency (RF)energy through the luminal surface of the renal artery.

The Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study of the safety and effectiveness of renal denervation in subjects with uncontrolled hypertension. Bilateral renal denervation will be performed using the Symplicity Catheter - a percutaneous system that delivers radiofrequency (RF)energy through the luminal surface of the renal artery.

Inclusion Criteria:

• Individual is ≥ 18 and ≤ 80 years old at time of randomization.
• Individual is receiving a stable medication regimen including full tolerated doses of 3 or more anti-hypertensive medications of different classes, of which one must be a diuretic (with no changes for a minimum of 2 weeks prior to screening) that is expected to be maintained without changes for at least 6 months.
• Individual has an office systolic blood pressure (SBP) of ≥ 160 mmHg based on an average of 3 blood pressure readings measured at both an initial screening visit and a confirmatory screening visit

Exclusion Criteria:

• Individual has an estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m2
• Individual has an Ambulatory Blood Pressure Monitoring (ABPM) 24 hour average SBP < 135 mmHg
• Individual has type 1 diabetes mellitus
• Individual requires chronic oxygen support or mechanical ventilation (e.g., tracheostomy, CPAP, BiPAP) other than nocturnal respiratory support for sleep apnea.
• Individual has primary pulmonary hypertension.
• Individual is pregnant, nursing or planning to be pregnant.