<p>Renal denervation (RDN) is recommended for the management of arterial hypertension. The aim of this study was to assess the cost-effectiveness of RDN. A systematic review/meta-analysis was conducted to identify RDN cost-effectiveness studies. The Incremental Cost-Effectiveness Ratio (ICER) per one Quality-Adjusted Life Year (QALY) gained (the extra cost needed for one additional year of good quality life) was compared to the respective country-specific Willingness to Pay (WTP) Thresholds (the maximum ICER/QALY gained that is considered acceptable by a healthcare system or organization for an intervention to be deemed cost-effective). Nineteen studies (16 countries) were included, all in favor of RDN cost-effectiveness. Most studies (<i>n</i> = 12/19, 63%) were conducted after 2024, half in the context of European economic/healthcare systems. All studies implemented decision-analytic Markov models and compared RDN (mainly radiofrequency) plus standard of care (SoC) vs SoC alone. Meta-analysis of 7 studies indicated a pooled ICER/QALY gained 22209 €, compared to WTP Threshold 50000 €, thereby indicating the cost-effectiveness of RDN. Meta-analysis of 19 studies indicated a pooled ICER/QALY gained to WTP Threshold ratio of 0.31 (0.20, 0.44). In sensitivity analyses RDN was shown to be cost-effective in both resistant and uncontrolled hypertensive patients, especially in those with high cardiovascular risk and considering longer time horizons. Most studies were deemed to have a low risk of bias. In line with guidelines recommendations, RDN appears to be a cost-effective intervention across a variety of clinical scenarios, both for patients with resistant or uncontrolled hypertension and especially in young and/or high cardiovascular risk patients.</p><p><b>Prospero Registration ID</b>: CRD420251133996</p><p></p>