Left ventricular (LV) hypertrophy and diastolic dysfunction predict long-term cardiovascular events. We evaluated whether multielectrode renal denervation (RDN) can provide beneficial cardiac adaptations in patients with resistant hypertension and LV hypertrophy long term at 24 months. Seventeen patients with true drug-resistant hypertension (age: 57 ± 9 years, 11 men, body mass index: 33.79 ± 5.49 kg m-2, office blood pressure (BP): 183 ± 20/97 ± 18 mm Hg and ambulatory BP: 152 ± 16/86 ± 15 mm Hg receiving 4.5 anti-hypertensive drugs per day) and LV hypertrophy underwent multielectrode RDN (EnligHTNTM, St Jude Medical). At baseline, LV mass index averaged 141.1 ± 16.8 g m-2 (58.4 ± 7.8 g m-2.7) and mitral lateral E/E’ 14.7 ± 6.2. At 6, 12 and 24 months after RDN, the LV mass/body surface area (LV mass per height2.7) reduced significantly by 9.1% (8.8%), 11.3% (10.5%) and 15.5% (14.1%), respectively; and the mitral lateral E/E’ reduced significantly by 14.0%, 15.3% and 29.7%, respectively. At 24 months after RDN, majority (70.6%) of the patients showed regression of LV hypertrophy of at least one level; the proportion of patients with concentric LV hypertrophy had dropped by 47.1% from baseline; and the proportion of patients with office systolic BP level of ≤ 160 mm Hg had dropped by 76.5% from baseline. No statistically significant association was observed between the changes in office BP and the changes in LV mass index or diastolic function. In patients with drug-resistant hypertension and LV hypertrophy, multielectrode RDN can contribute to significant and sustained improvements of diastolic dysfunction and attenuation of LV mass indices long term at 24 months.