Objective To observe the effectiveness of catheter-based renal sympathetic denervation (RDN) for reducing blood pressure in patients with resistant hypertension using a 5 F microtube-irrigated ablation catheter. Methods Thirty patients with resistant hypertension received RDN between January 2013 and December 2015. They were randomly divided into two groups:general ablation catheter group and microtube-irrigated ablation catheter group, with 15 cases in each group. 5 F temperature-controlled catheter was used in the general ablation catheter group. 5 F microtube-irrigated ablation catheter (microtubes at the head) was used in the microtube-irrigated ablation catheter group. Cold saline was irrigated for mapping and ablation. All patients were followed up for 9 months. Clinic blood pressure, 24 h ambulatory blood pressure, biochemical tests and cardiac function were measured at baseline and during follow-up. Results RDN was successfully performed in all patients. At the 9-month follow-up, the decrease of 24 h ambulatory systolic blood pressure (SBP) in the microtube-irrigated ablation catheter group was more obvious than that in the general ablation catheter group ([34.67±13.02] mmHg vs[17.00±16.74] mmHg, P<0.01; 1 mmHg=0.133 kPa). The 24 h ambulatory diastolic blood pressure (DBP) in the microtube-irrigated ablation catheter group was significantly lower than that in the general ablation catheter group ([81.20±7.15] mmHg vs (87.60±8.17) mmHg, P<0.05). There was a decreased trend in the use of antihypertensive drugs in the microtube-irrigated ablation catheter group as compared with the general ablation catheter group, particularly in the use of diuretics (P<0.05). During the operation, the microtube-irrigated ablation catheter group had a significantly lower catheter temperature (P<0.001), greater energy (P<0.05), and greater decrease in impedance than the general ablation catheter group (P<0.05). No syncope or amaurosis caused by hypotension, or deterioration of renal function occurred in either group. Conclusion 5 F microtube-irrigated ablation catheter is a safe and effective device during renal artery ablation. It has more advantages than general ablation catheter in reducing SBP and diuretic use in the treatment of resistant hypertension.