Comparative efficacy and safety of renal denervation (RDN) interventions for uncontrolled (UH) and resistant hypertension (RH) is unknown. We assessed the comparative efficacy and safety of existing RDN interventions for UH and RH. Six search engines were searched up to 1 May 2020. Primary outcomes were mean 24-h ambulatory and office systolic blood pressure (SBP). Secondary outcomes were mean 24-h ambulatory and office diastolic blood pressure (DBP), clinical outcomes, and serious adverse events. Frequentist random-effects network meta-analyses were used to evaluate effects of RDN interventions. Twenty randomized controlled trials (RCTs) (n = 2152) were included, 15 in RH (n = 1544) and five in UH (n = 608). Intervention arms included radiofrequency (RF) in main renal artery (MRA) (n = 10), RF in MRA and branches (n = 4), RF in MRA+ antihypertensive therapy (AHT) (n = 5), ultrasound (US) in MRA (n = 3), sham (n = 8), and AHT (n = 9). RF in MRA and branches ranked as the best treatment to reduce 24-h ambulatory, daytime, and nighttime SBP and DBP versus other interventions (p-scores: 0.83 to 0.97); significant blood pressure effects were found versus sham or AHT. RF in MRA+AHT was the best treatment to reduce office SBP and DBP (p-scores: 0.84 and 0.90, respectively). RF in MRA and branches was the most efficacious versus other interventions to reduce 24-h ambulatory SBP and DBP in UH or RH.