Uremia is associated with platelet dysfunction and can cause a bleeding tendency resulting in a major bleeding event after an invasive procedure or surgery that may be aggravated by antiplatelet agents. We prospectively investigated the potential of desmopressin to improve platelet dysfunction and to lower bleeding risk after emergent invasive procedures in uremic patients taking antiplatelet drugs. Twenty-three patients were enrolled with a mean age of 60.2 ± 11.7 years. Baseline blood urea nitrogen and creatinine were 70.5 ± 29.4 and 10.02 ± 4.52 mg/dL, respectively. Twenty-one patients took aspirin. All patients were infused with desmopressin before their invasive procedures, which were a central catheter insertion for emergent hemodialysis in 13 patients, percutaneous nephrostomy in 7 patients, and angiography through arm or leg vessels in 3 patients. After desmopressin infusion, both the hematocrit and platelet count were slightly decreased without changes in prothrombin time or activated partial thrombin time. Collagen/epinephrine-closure time was significantly shortened from 252.7 ± 40.7 to 144.6 ± 51.0 s (p < 0.001). There were minimal bleeding in 20 patients and mild bleeding in 3 patients. None experienced severe bleeding event or required additional intervention for bleeding control. There were no adverse events including the decrease of serum sodium concentration. In conclusion, a single infusion of desmopressin before invasive procedures in uremic patients on antiplatelet drugs appeared to be well tolerated and improved platelet dysfunction measured by collagen/epinephrine-closure time.