Objective To evaluate the effect of perioperative administration of desmopressin on perioperative bleeding and postoperative blood test indexes in patients receiving varicose vein, urological and orthopedic surgeries. Methods This prospective study randomly enrolled 182 patients who underwent great saphenous varicose vein surgery, or urological or orthopedic surgery in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences, Beijing Cancer Hospital, Shengjing Hospital of China Medical University, Shandong Provincial Hospital, and Linyi Municipal People′s Hospital between January 2018 and July 2019. The patients were randomly divided into desmopressin group (n=98) and control group (n=84), each group being further divided into three subgroups:varicose vein surgery, orthopedic surgery, and urological surgery. The two groups were compared in hemoglobin, platelets, sodium, alanine aminotransferase, serum creatinine, prothrombin time(PT), D-dimer, activated partial thromboplastin time (APTT), fibrinogen(Fb), postoperative hemorrhages, intraoperative bleeding volume and postoperative ecchymosis area. SPSS 26.0 was used for statistical analysis. Data comparison between two groups was performed usingχ²test, U test, t test or Fisher exact test. Results On postoperative day 1, Na⁺ level in the varicose vein and orthopedic surgery subgroups, APTT in the varicose surgery subgroup, and PT in the orthopedic surgery subgroup were all lower in the desmopressin group than in the corresponding subgroups of the control group, the differences being statistically significant (P<0.05 for all). On postoperative day 2, Na⁺ and Fb in the varicose vein and orthopedic surgery subgroups were lower in the desmopressin group than in those of the control group, the differences being statistically significant (P<0.05 for all). Serum creatinine in the control group was lower on postoperative day 1 and 2 than that before the surgery with statistically significant differences (P<0.05 for all). There was no significant differences in other indexes. Postoperative ecchymosis occurred in more patients in the varicose vein surgery subgroup of the desmopressin group [16(32.7%)] than that of the control group [16(41.0%)], and the single area of ecchymosis in the desmopressin group [0.220 cm² (0.155 cm², 0.580 cm²)] was significantly lower than that in the control group [0.315 cm²(0.163 cm²,1.475 cm²)], with a statistically significant difference (P<0.05). Conclusion The perioperative use of desmopressin affects blood indexes, effectively reducing the area of postoperative ecchymosis in large saphenous varicose veins and the incidence of bleeding and deep vein thrombosis.