The effect of desmopressin on platelet function in patients with continued antiplatelet therapy undergoing cardiac surgery is discussed controversially. We assessed platelet reactivity in 86 patients undergoing elective coronary artery bypass grafting (CABG) under extracorporeal circulation. Twenty-nine of these patients were without preoperative antiplatelet therapy (group A), while 57 were treated with acetylsalicylic acid (ASA) 100 mg qd up to the day of surgery. Out of this cohort, 24 patients received no desmopressin perioperatively (group B), whereas 33 patients were treated with desmopressin 0.4 microg/kg after administration of protamine due to increased bleeding tendency (group C). Multiple electrode platelet aggregometry with arachidonic acid as agonist showed a marked decrease of platelet reactivity in patients without antiplatelet therapy immediately after extracorporeal circulation compared to preoperative control (375 ± 227 vs. 749 ± 330 AU*min, p<0.001). Platelet reactivity recovered to preoperative controls in group A at 24 hours after protamine administration (662 ± 295 AU*min). Platelet reactivity in patients on ASA was not decreased further after extracorporeal circulation (group B: 197 ± 126 vs. 251 ± 203 AU*min, p=0.14; group C: 212 ± 100 vs. 245 ± 248 AU*min, p=0.43) and improved significantly within 24 hours. A statistically significant effect of desmopressin, however, could not be determined (group B: 392 ± 223 AU*min; group C: 439 ± 324 AU*min at 24 hours after protamine, p=0.63 for between-subjects contrast). Our data suggest that desmopressin does not affect platelet reactivity in patients on ASA undergoing CABG and is, therefore, not useful in this clinical setting.