Abstract: Objective To explore the efficacy and safety of renal denervation（RDN） guided by three-dimensional mapping system in young and middle-aged patients with hypertension. Methods A total of 24 young and middle-aged patients with primary hypertension were included, who underwent RDN using pressure sensing cold saline infusion catheter guided by CARTO three-dimensional mapping system at the Department of Cardiology of the First Affiliated Hospital of Xiamen University, from March 2022 to March 2023. All patients underwent strict lifestyle management for six months before receiving RDN. Using a self-controlled design to observe the surgical-related complications of RDN and assess the effects on patients’ office blood pressure, office heart rate, 24-hour ambulatory blood pressure, 24-hour average heart rate, home blood pressure, home heart rate and the anti-hypertensive therapeutic intensity score at baseline, 1 week, 1 month, and 6 months after surgery. Additionally, evaluations were performed on serum creatinine, serum urea, urinary microalbumin, urinary microalbumin-to-creatinine ratio, glomerular filtration rate, and renal artery morphology. Results All 24 patients successfully completed RDN, with an average of（12.1±3.4） and（12.8±2.6） ablation points on the left and right renal arteries, respectively. Among the 24 patients, there was 1 case of renal artery branch intramural hematoma and 1 case of dissection（a total of 8.3%）, and no severe complications such as renal artery main branch dissection, rupture, or stenosis were observed. 16 cases（66.7%） showed local ecchymosis at the puncture site of the femoral artery, without arteriovenous fistula or hematoma. All patients continued strict lifestyle management after RDN. Comparison with pre-RDN, patients exhibited a significant decrease in office blood pressure, office heart rate, 24-hour average blood pressure, 24-hour average heart rate, and home blood pressure and home heart rate（all P＜0.05）, and the anti-hypertensive therapeutic intensity score decreased（the scores were 0.96±0.06, 0.89±0.04, 0.73±0.04 and 0.48±0.09 at baseline, 1 week, 1 month, and 6 months after surgery respectively, F=17.851, P＜0.001）, but there was no statistically significant difference in renal function related indicators（all P＞0.05）, and there was no abnormality in renal artery morphology at the 6-month follow-up. Conclusion In young and middle-aged patients with hypertension, the application of RDN using pressure sensing cold saline infusion catheter guided by CARTO three-dimensional mapping system contributes to further blood pressure reduction with safety.