OBJECTIVES: Catheter-based renal denervation (RDN) is a new approach to treat resistant hypertension, a condition that affects approx. 10-15% of hypertensives. Our objective was to develop a decision-analytic model to assess clinical and cost-effectiveness of (RDN) from the U.K. National Health Service perspective. METHODS: A 34-state Markov model predicted cardiovascular endpoints, mortality, quality-adjusted life years (QALYs), and costs. Input parameters were derived from multivariate risk equations and other published sources, including the recently published NICE Hypertension Guidance. We evaluated the impact of a 32 mmHg reduction in systolic blood pressure (SBP), from a baseline SBP of 178 mmHg, in a 42.5% female, 34% diabetic, and 16% smoking cohort with a mean age of 58, as observed in the Symplicity HTN-2 randomized controlled trial. We calculated ten-year relative risks and the lifetime incremental cost-effectiveness ratio (ICER) in £/QALY discounted at 3.5% per year for numerator and denominator. RESULTS: Relative risks for clinical endpoints were 0.70 for stroke, 0.68 for myocardial infarction, 0.78 for all coronary heart disease, 0.79 for heart failure, 0.72 for end-stage renal disease, 0.65 for cardiovascular and 0.82 for all-cause mortality, respectively. The ICER was £4,870/QALY. CONCLUSIONS: Our model projections suggest RDN reduces and delays cardiovascular events and is a cost-effective therapy in the U.K..