Abstract Body (Do not enter title and authors here): Introduction: New therapies for resistant hypertension (RH), including renal denervation (RDN), have been studied. Aim: Access the safety and effectiveness of radiofrequency-based RDN vs pharmacological treatment for RH. Methods: A thorough literature search was conducted across PubMed, EMBASE, and the Cochrane databases, focusing on studies that compared the effects of radiofrequency-based RDN versus pharmacological treatment for RH. Treatment effects for binary and continuous endpoints were pooled and used, respectively, odds-ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) to analyze continuous outcomes. Results: All the 10 included studies were randomized controlled trials, they involved 1.182 patients, and 682 received radiofrequency-based RDN. The follow-up period ranged from 6 to 84 months. Analysis revealed that the RDN group had a significant reduction in office systolic blood pressure (BP) (MD: -9.5 mmHg; 95% CI: -16.81 to -2.29; P=0.01), office diastolic BP (MD: -5.1 mmHg; 95% CI: -8.42 to -2.80; P<0.001), 24 h systolic BP (MD: -4.8 mmHg; 95% CI: -7.26 to -2.42; P<0.001). For 24 h diastolic BP RDN did not have a significant reduction (MD: -2.3 mmHg; 95% CI: -4.19 to -0.52; P=0.012). The heterogeneity between the studies was high, visible in the funnel and Baujat plots. The OR was non-significant for non-serious adverse events, but also clinically significant for hypertensive crises and strokes for the RDN group. Conclusions: While the pharmacological regimen of 3 or more anti-hypertensive, including a diuretic, still be the first-line option for RH treatment, our results support that radiofrequency-based RDN is superior in reducing global BP and is safe.