Background: This meta-analysis was designed to evaluate the antihypertensive efficacy of intravascular renal denervation (RDN) in patients with essential hypertension, especially to determine the magnitude of blood pressure (BP) reduction with RDN therapy using second-generation catheters. Methods: PubMed was searched to identify randomized sham-controlled trials from inception through August 2021. The endpoints were changes in 24-hours (24-h) ambulatory BP or office BP (OBP). This meta-analysis was performed by calculating the weighted mean difference (WMD) with 95% confidence interval (CI) using the random-effects model when the I2 index was < 50%. Fixed-effects model was used when the I2 index was ≥ 50%. Results: A total of 1297 patients were included in 8 randomized, sham-controlled trials in this meta-analysis. Intravascular RDN reduced 24-h ambulatory systolic BP (SBP) −3.02 (WMD, 95% CI, −4.95, −1.10, p <0.01,) and diastolic BP (DBP) −1.66 (WMD, 95% CI, −2.44, −0.88, p<0.001) mm Hg, respectively. In the studies using first-generation catheters, the WMD of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham-control were −2.67 (95% CI, −5.08, -0.27; P<0.05) and −0.82 (95% CI, −2.19, 0.56; P>0.05) mm Hg. In the studies using second-generation catheters, the WMD of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham-control were −3.14 (95% CI, −5.94, −0.33, p<0.05) and –2.06 (95% CI, −3.02, −1.11, p<0.001) mm Hg. Intravascular RDN using second-generation catheters reduced office SBP −6.30 (WMD, 95% CI, −7.67, −4.93, p<0.001) and DBP −3.88 (WMD, 95% CI, −4.44, −3.33, p<0.001) mm Hg, respectively. Conclusions: Intravascular RDN using second-generation catheters reduces ambulatory and office BP in patients with essential hypertension. The selection of appropriate hypertensive patients may be the major challenge for the performance of intravascular RDN in routine clinical practice.