OBJECTIVE The aim of this study was to investigate whether renal sympathetic denervation (RSD) is more effective on myocardial hypertrophy than the angiotensin-converting enzyme inhibitor (ACEI) perindopril in spontaneously hypertensive rats (SHRs). METHODS After bilateral renal denervation blood pressure (BP) was measured every 10 days. On day 50 the heart was (histo)pathologically examined. The ventricular weight to body weight ratios (VW/BW), myocardial diameter and collagen volume fraction (CVF) were calculated, and cardiac hypertrophy marker genes were analyzed by RT-PCR. RESULTS At the baseline evaluation all groups had comparable BP. After treatment the BP of the RSD group was significantly reduced (p < 0.05). The BP of the RSD group was lower than that of the perindopril group on days 10, 20 and 30th (p < 0.05) but on day 50 systolic BP of the RSD group was significantly higher (p < 0.05) whereas there were no significant differences in diastolic BP. The VW/BW decreased in the RSD group, whereas the value did not change significantly in the perindopril group. The myocardial diameter of the left ventricular cardiomyocytes was also significantly lower in the RSD group and stayed the same in the perindopril group. Collagen volume fraction (CVF) in the RSD group was significantly lower than in the perindopril group (p < 0.05). Significant changes in the expression levels of NPPA, MYH7, and MYH6 (P < 0.05) were observed in the RD-SHR groups (p < 0.05). There was a significant difference in the expression level of MYH6 (p < 0.05) between the RSD group and the perindopril group but the expression levels of NPPA and MYH7 were not significantly different. CONCLUSIONS In this study, RSD had a significant antihypertensive effect and inhibited hypertensive-induced cardiac hypertrophy in SHRs and showed advantages compared with ACEI in decreasing BP in the early stage and in inhibiting myocardial fibrosis.