Background: Uterine leimyomas are tumors of the smooth muscles and the connective tissues of the uterus. They are considered to be the most common benign pelvic tumor affecting about 20% of women above the age of 35. The diverse symptomatology of fibroids can be attributed to size, number and location of the tumors. The common symptoms include menorrhagia, infertility, abdominal mass and pressure effects. Aim of the Work: The aim of this study is to compare between the effect of medical (preoperative vaginal misoprostol) and non-medical (bilateral uterine artery ligation) regarding their efficacy to decrease blood loss in trans-abdominal myomectomy. Patients and Methods: Prospective randomized controlled interventional clinical trial. . It included 60 women recruited from those attending the outpatient gynecology clinic, seeking treatment for symptomatic uterine myomas. Results: The current study revealed that there was no statistically significant difference between both groups regarding operative time, blood loss and postoperative hospital stay. Conclusion: A single pre-operative dose of 400 micrograms of vaginal misoprostol is as effective as uterine artery ligation in decreasing blood loss in transabdominal myomectomy. Misoprostol is a simple, cheap, fast, available and applicable tool that can be administered even an hour preoperatively. Recommendations: Preoperative vaginal misoprostol is an effective practical tool in decreasing blood loss in transabdominal myomectomy. Investigation of misoprostol use in larger population groups and with different dosages and administration routes, together with comparison of other methods used to reduce bleeding during myomectomy, is recommended.