Objective To evaluate the influence of perioperative application of desmopressin (DDAVP) on the perioperative bleeding and thrombogenesis in great saphenous varicose vein surgery. Methods From January 2015 to September 2016,6 patients undergoing great saphenous varicose vein surgery from 6 medical centers were enrolled in this prospective randomized controlled trial, and randomly divided into the DDAVP group (n=81) and the blank control group (n=85). The indicators, such as hemoglobin (Hb), platelet (PLT), alanine aminotransferase (ALT), serum creatinine (SCr), activated partial prothrombin time (APTT), D-dimer, von Willebrand factor (vWF), postoperative ecchymosis area, and incidences of lower extremity deep venous thrombosis and major bleeding events, were compared between the 2 groups. Clinical data were analyzed by SPSS statistics 22.0. The differences were compared with t test, rank-sum test (Mann-Whitney U test), Chi-square test or Fisher exact test, respectively. Results The ecchymosis area was significantly smaller in the DDAVP group than the blank control group [1.92(0.42,0.83) vs 6.00(1.82,9.60)cm²; P<0.05]. DDAVP could effectively reduce the large ecchymosis in the elderly older than 60 years. One case of deep venous thrombosis occurred in the control group, but none in the DDAVP group. There were no significant differences in postoperative Hb, PLT, ALT, APTT, D-dimer and vWF between the 2 groups(P>0.05). Conclusion Perioperative DDAVP can efficiently decrease perioperative ecchymosis area in the patients treated with varicose vein surgery, and doesn’t increase the incidences of postoperative bleeding and venous thromogenesis.