Background/Aims: Desmopressin decreases bleeding time in uremic patients. Although bleeding time is the most frequently used measure of global platelet function, this test has important disadvantages. In vitro closure time (CT) is a relatively new and efficient test of primary hemostasis. We designed a prospective randomized study to evaluate the effect of desmopressin on platelet function, as measured by in vitro CT, in uremic patients. Methods: Forty-eight uremic patients, about to commence hemodialysis and with prolonged CT, were randomized to infusion with desmopressin (n = 24) or saline alone (n = 24). Complete blood count, prothrombin time, activated partial thrombin time, levels of plasma fibrinogen, von Willebrand factor (VWF), factor VIII (FVIII) and CT were measured before and 1 h after desmopressin or saline infusion. Results: Following desmopressin infusion, collagen/epinephrine and collagen/adenosine diphosphate CT were significantly shortened from 212 ± 58 to 152 ± 45 s (p = 0.01) and from 189 ± 78 to 147 ± 58 s (p = 0.012), respectively; levels of FVIII and VWF were significantly increased from 188 ± 66 to 252 ± 93% (p = 0.017) and from 113 ± 9 to 121 ± 9% (p = 0.043), respectively. There were no significant changes in the control group. Conclusions: Desmopressin improved platelet dysfunction and increased the plasma concentrations of VWF and FVIII, suggesting that desmopressin may play a role in improving the bleeding tendency in uremic patients.