Τo investigate whether the use of vasopressin played an important role in the safe expansion of the indications of laparoscopic myomectomy in our practice. A retrospective comparison of prospectively collected data (Canadian Task Force classification II2). A gynecologic endoscopy unit in a tertiary university hospital. One hundred fifty patients undergoing laparoscopic myomectomy; 50 were treated without the use of any vasoconstrictive agent (group 1), and 100 were treated with intraoperative intramyometrial injection of dilute vasopressin (20 IU/100 mL normal saline) (group 2). Laparoscopic myomectomy. We compared the 2 groups in terms of size, number, and type of myomas; estimated blood loss (EBL); procedure length; transfusion rates; laparoconversion rates; and rates of complications. Two cases in group 1 (4%) were laparoconverted versus none (0%) in group 2. Overall, the mean EBL was 321.8 ± 246.0 mL in group 1 compared with 147.8 ± 171.8 mL in group 2, respectively (p <.001). Additionally, EBL was significantly lower in the vasopressin group in all of the study's subgroups of patients stratified according to the size and number of myomas. Procedure length did not differ significantly between the 2 groups (130.8 ± 49.5 vs 115.6 ± 49.4 minutes, p = .078). The risk factors for prolongation of the procedure included size and number of myomas independently of vasopressin. The rates of hypercapnea and subcutaneous emphysema were higher in group 1. The risk factors for hypercapnea and subcutaneous emphysema included the size and intramural position of the largest myoma. Vasopressin was not associated with serious cardiovascular adverse events. Vasopressin is effective in reducing blood loss during laparoscopic myomectomy. Although experienced surgeons may achieve comparable operation times without vasopressin, even in the most challenging cases, blood loss may still be considerable. The occurrence of hypercapnea is higher in untreated cases and may contribute to laparoconversion.