Background: Open myomectomy remains the key alternative that has been shown to have a satisfactory outcome in terms of fertility preservation and symptom resolution, particularly when the number and size of leiomyomas do not permit any other surgical route of surgery. This work aimed to reduce blood loss during myomectomy using either intravenous or topical methods. Methods: This randomized controlled trial included 60 Patients who undergo abdominal myomectomy with myoma staging from (3 to 6) according to FIGO staging divided into three groups each group comprised of 20 patients. Group I: received 110 ml normal saline intravenous just before skin incision. Group II: 1g tranexamic acid intravenous just before skin incision. Group III: received 2g topical tranexamic acid applied on myoma bed after myomectomy. The primary outcome was total blood loss estimation intra-operative, and postoperative. Results: there was a statistically significant difference between the studied groups regarding blood loss with higher blood loss intraoperative, postoperative on control, and topical than intravenous tranexamic acid group (p-value= 0.8, 0.9 and 0.9) respectively. Regarding the need for blood transfusion where (50.0%) of the control group needed blood transfusion while only (10.0%) of intravenous and topical tranexamic acid groups needed blood transfusion (p-value= 0.003*). Conclusions: Intravenous and topical tranexamic acid safe and reliable method to help decrease blood loss during open myomectomy without serious side effects.