Abstract Background and Aims Percutaneous kidney biopsy remains the gold standard for diagnosis of kidney disease. The incidence of bleeding complications following kidney biopsy ranges from 13 to 34%. This study aimed to evaluate the effect of prebiopsy administration of intranasal desmopressin on the incidence of post-biopsy bleeding complications in patients undergoing ultrasound-guided percutaneous native kidney biopsy with an estimated GFR of 60 ml/min/1.73 m2. Method It was a single-centre, double-blind, randomized controlled trial. Patients undergoing percutaneous ultrasound-guided biopsy of the native kidney in the department with age >18 years, BP before biopsy ≤140/90 mm Hg, and eGFR < 60 mL/min/1.73 m2. The patients were divided into experimental (intranasal desmopressin) and control group (intranasal normal saline), and block randomization was done by a computer-generated random number list prepared by an investigator with no clinical involvement in the study into an experimental and control group. The experimental group was treated using intranasal desmopressin acetate (dosage of 3 mcg/kg, each puff delivering 10 mcg) 1 hour before the kidney biopsy. The control group was treated with a placebo (equivalent dose of intranasal saline)(CTRI/2023/01/048812) Results A total of 152 patients were included (78 male and 74 female), the experimental group had 74 patients, and the control group had 78 patients. The mean age was 39.08 ± 15.03 yrs and 38.83 ± 15.67 yrs., respectively (p = 0.921). The experimental group had significantly less hematoma formation at 24 hrs. post kidney biopsy compared to the control group (p = 0.019). The hematoma volume at six hrs. (p = 0.342) and 24 hrs. (p = 0.698); post-kidney biopsy was not different between the two groups. Conclusion Intranasal desmopressin administration effectively reduces post-biopsy native kidney peri-renal hematoma formation at 24 hrs post-procedure. However, other bleeding complications were not different in the two groups of our studies.