<h2 id="hl0000489">Abstract</h2> <h2 id="hl0000491">Background</h2> <p id="hl0000492">Renal sympathetic denervation (RDN) reduces blood pressure (BP).</p> <h2 id="hl0000494">Methods</h2> <p id="hl0000495">This single-arm open-label study enrolled patients with resistant hypertension (RH) and treat them by CT-guided ozone mediated lumbar-renal sympathetic denervation (L-RDN). The primary endpoint was to assess the changes of BP over 24-h ambulatory BP monitoring (ABPM) and to evaluate the anti-hypertensive medication burden (AHMB) at 3-month follow-up. This study was registered in Chictr.org.cn (ChiCTR2300071375).</p> <h2 id="hl0000497">Results</h2> <p id="hl0000498">17 patients (mean age 65.12 ± 10.77 years) with AHMB of 4.12 ± 1.11 were enrolled. After the procedure, 7 patients (46.7 %) matched the criteria for antihypertensive medication reduction. The AHMB decreased to 3.87 ± 0.96 for the whole objectives and from 3.87 ± 0.96 to 3.55 ± 0.78 for patients with normal baseline renal function. On top of the lessened AHMB, L-RDN further reduced morning systolic BP (SBP) by −8.6 ± 4.0 mmHg (<span> </span><i>p</i><span> </span>= 0.034) and diastolic BP (DBP) by −4.6 ± 2.1 mmHg (<span> </span><i>p</i><span> </span>= 0.032) for all participants and morning SBP by −13.2 ± 3.6 mmHg (<span> </span><i>p</i><span> </span>< 0.001), morning DBP by −6.2 ± 2.4 mmHg (<span> </span><i>p</i><span> </span>= 0.011) and daytime SBP by −4.1 ± 1.6 mmHg (<span> </span><i>p</i><span> </span>= 0.009) for those with normal baseline renal function at 3-month of follow-up. No adverse events were reported intra- and post operation.</p> <h2 id="hl0000505">Conclusions</h2> <p id="hl0000506">CT-guided ozone-mediated L-RDN might be an innovative approach of RDN for treating RH. Confirmatory studies are warranted.</p>