Purpose <p>This study aimed to evaluate the effectiveness of intranasal desmopressin in reducing exit-site bleeding during the placement of tunnelled dialysis catheters.</p> Methods <p>This open-label randomised controlled trial was done on patients aged ≥ 12 years undergoing placement of tunnelled dialysis catheters. Exclusion criteria included current use of anticoagulants, platelet count &lt; 50 × 10⁹/l, previous tunnelled dialysis catheter insertions at the same site, blood pressure &gt; 180/110 mmHg, and unwillingness. Patients in the intervention arm were administered intranasal desmopressin, 10 μg in each nostril, 30&#xa0;min before the procedure. Patients in the control arm did not receive desmopressin. All patients were monitored for bleeding from the TDC exit site for 24 h after the procedure. For persistent bleeding, a purse-string suture was applied approximately 1 cm from the exit site.</p> Results <p>There were 86 patients aged 56.41 ± 15.64 years. The majority of the catheters (79; 91.86%) were placed in the right internal jugular vein. In the intervention arm, six patients (13.95%) experienced bleeding from the catheter exit site, compared to eleven patients (25.58%) in the control arm (p = 0.176). Purse-string suturing was required for six (13.95%) patients in the intervention arm and ten (23.26%) patients in the control arm (p = 0.268). No patient reported significant side effects.</p> Conclusion <p>There was a statistically insignificant reduction in exit-site bleeding with intranasal desmopressin.</p> <p><i>Trial registry</i>: Iranian Clinical Trial Registry (IRCT20240215061017N2)</p>