Objective To explore the feasibility of the catheter-based renal sympathetic denervation (RDN) guided by monitoring fractional flow reserve (FFR) with pressure guide wire. Methods Eleven minipigs were allocated into RDN group (n=8) and sham operation group (n=3). Before ablation, the angiography of bilateral renal arteries was conducted. Ablation catheter and FFR pressure guide wire were implanted in the renal arteries guided by 7F guided catheter. Then renal arteries were observed by X-ray. The FFR value (renal artery pressure/aortic pressure) was monitored by electric stimulation (20 Hz). When the FFR value had significant change, the target was to be ablated (50℃, 10 W, 60 s). The ablation was considered effective once there was no change of the above indicators after a second stimulation immediately following ablation. Results Renal artery ablation was successfully completed in all the 8 pigs of RDN group. FFR values were monitored before and after ablation, and the results showed that the FFR values were significantly decreased upon stimulation before RDN (0.73±0.07 vs 0.98±0.02, P<0.01), and the FFR values were almost unchanged immediately after ablation (0.97±0.03 vs 0.95±0.02, P=0.25), which was not observed in the sham operation group. Conclusion There is significant difference in the FFR values of the target following stimulation before and after RDN. The FFR pressure guide wire-mediated target ablation may become a new operation mode, with its effectiveness and mechanism needed to be further verified.