Abstract Background/Introduction Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN emerges as an alternative for patients with resistant arterial hypertension. Despite this, the clinical efficacy of RDN is still not fully understood. Purpose Therefore, we aimed to compare the use of renal denervation versus sham procedure or pharmacological treatment in patients with resistant HTN. Methods We performed a systematic search of PubMed, Embase, Cochrane databases for randomized controlled trials (RCTs) comparing the use of renal denervation procedures and sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using R Studio 4.3.2. Heterogeneity was examined with the Cochran Q test I² statistics. Mean difference (MD) with 95% CI were pooled across trials. P values of < 0.05 were considered statistically significant. The primary continuous outcomes of interest were change from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP) and serum creatinine. Results Twenty-one RCTs reporting data on 3345 patients were included in this meta-analysis. Among them, 2004 (59,91%) received renal denervation and 1341 (40,09%) received pharmacological treament or sham procedure. Follow-up ranged from 2 to 48 months. The mean age of patients between studies ranged from 50.7 to 65 years. Compared to control group, RDN significantly reduced Systolic Blood Pressure (SBP) (MD -3.53 mmHg; 95% CI -5.94 to -1.12; I2 = 74%) and Diastolic Blood Pressure (DBP) (MD -1.48 mmHg; 95% CI -2.56 to -0.40; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; I2 = 40%) there was no significant difference between RDN and control groups. Conclusion In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with a reduction in SBP and DBP compared to sham procedure or pharmacological treatment.