Abstract BACKGROUND Renal denervation (RDN) is effective at reducing blood pressure (BP) among patients with treatment-resistant hypertension (TRH). However, recent findings regarding the effectiveness of RDN for BP reduction compared with standard treatment of care (SoC) has initiated a rigorous debate about its role in TRH management. In this study, we sought to determine the thresholds for cardiovascular risk and costs of RDN which would make RDN cost-effective. METHODS A Markov model was constructed to simulate cardiovascular events over a lifetime among TRH subjects aged 60 years at baseline, and without prior cardiovascular disease. The effect on lowering BP was based on results observed in clinical trials of RDN undertaken to date, and the expected subsequent change to cardiovascular risk was drawn from a published meta-regression. Cost and utility data were drawn from published sources. Incremental cost-effectiveness ratios (ICER) in terms of Australian dollars (AUD) per life year and per quality-adjusted life year (QALY) gained were estimated to assess RDN cost-effectiveness relative to SoC from the Australian health care perspective, assuming a willingness-to-pay threshold of AUD 50,000. RESULTS Over a lifetime horizon, the model predicted that at the current estimated costs of RDN (AUD 9531/€6573, 1€ = 1.45 AUD), it would be cost-effective only if it was targeted to patients whose 10-year predicted cardiovascular risk was at least 13.2% initially. The ICERs (discounted) were AUD 49,519 per life year gained and AUD 47,130 per QALY gained. CONCLUSIONS At current costs and based on currently observed effects on BP reduction, RDN would be cost-effective among patients with TRH.