The purpose of this First-in-Human Clinical investigation is to evaluate the safety and performance of the St. Jude Medical EnligHTN™ Generation 2 Renal Denervation System for the treatment of patients with drug-resistant uncontrolled hypertension.

Inclusion Criteria:

• Subject is ≥ 18 and ≤ 80 years of age at time of consent
• Subject must be able and willing to provide written informed consent
• Subject must be able and willing to comply with the required follow-up schedule
• Subject has office Systolic Blood Pressure ≥ 160 mmHg at confirmatory visit
• Subject has a daytime mean Systolic Ambulatory Blood Pressure > 135 mmHg during the two week screening period
• Subject has an office Systolic Blood Pressure that remains ≥160 mmHg despite the stable use of ≥3 antihypertensive medications concurrently at maximally tolerated doses, of which one is a diuretic or subject was previously on diuretic but documented to be diuretic intolerant, for a minimum of 14 days prior to the procedure and with an expectation to maintain for a minimum of 180 days post procedure.

Exclusion Criteria:

• Subject has significant renovascular abnormalities such as renal artery stenosis > 30% in either renal artery
• Subject has undergone prior renal angioplasty, renal denervation, indwelling renal stents, and/or abdominal aortic stent grafts
• Subject has hemodynamically significant valvular heart disease as determined by the Study Investigator
• Subject has a life expectancy less than 12 months, as determined by a Study Investigator
• Subject is participating in another clinical study which has the potential to impact their hypertension management (pharmaceutical/device/homeopathic)
• Subject is pregnant, nursing, or of childbearing potential and is not using adequate contraceptive methods
• Subject has active systemic infection
• Subject has renal arteries with diameter(s) < 4 mm in diameter or <20 mm in length
• Subject has an estimated Glomerular Filtrate Rate (eGFR) <45 mL/min per 1.73 m2 using the Modified Diet in Renal Disease (MDRD) formula
• Subject has Diabetes Mellitus Type I
• Subject has multiple main renal arteries in either kidney
• Subject has an identified secondary cause of hypertension (for example, including, but not limited to, Polycystic kidney disease, Cushing's syndrome, Aldosteronism)
• Subject has evidence of significant abdominal aortic aneurysm (defined as maximum diameter of >4 cm)
• Subject has had a myocardial infarction, unstable angina pectoris or cerebrovascular accident less than 180 days prior to enrollment
• Subject is expected to have cardiovascular intervention within the next 180 days
• Subject has a condition which would interfere with the accurate interpretation of the study objectives including but not limited to a large arm diameter that is unable to accommodate the blood pressure cuff or arrhythmia that interferes with automatic pulse sensing.