Background/Aims: Intraoperative blood loss of more than 400 ml during gastrointestinal surgery is an independent predictor of mortality. Desmopressin acetate (1-deamino-8-D-arginine vasopressin [DDAVP]) could reduce perioperative blood loss. Few studies have prompted concerning the effects of DDAVP on gastrointestinal surgery. This study aimed to investigate whether DDAVP can decrease blood loss in patients with massive hemorrhage undergoing gastrointestinal surgery.Materials and Methods: A multiple-center, double-blind clinical trial was conducted; patients who underwent gastrointestinal surgery were recruited from three hospitals and were randomly assigned to two different groups. Patients in the treatment group received desmopressin in a dosage of 0.3 μg kg–1, 30 min once a day after the surgery; patients in the control group received 50 ml saline for 30 min. The primary outcome was the changes of hemoglobin at 24 h after the surgery, and the secondary outcomes included coagulation function, urine volume, serum creatinine, and safety.Results: There were 59 patients enrolled between June 1, 2015, and June 1, 2017. At 24 h after the surgery, the decrease in hemoglobin in the DDAVP group was significantly lower than that in the Normal Saline (NS) group (–5.0±6.9 g l–1 versus –10.2±9.3 g l–1, p=0.03). Sonoclot® showed that the platelet function in the DDAVP group was higher than that in the NS group at 24 h (2.56±0.59 versus 1.91±0.72, p<0.05). There was no difference in urine volume and serum creatinine at 24 h between the two groups.Conclusion: DDAVP could reduce post-operation blood loss in patients with massive hemorrhage undergoing surgery by improving the platelet function. We observed no difference in urine volume and serum creatinine in two groups.