Background: Cesarean myomectomy is a high-risk surgical procedure associated with significant intraoperative blood loss. Tranexamic acid (TXA), an antifibrinolytic agent, has shown efficacy in reducing perioperative blood loss in various obstetric surgeries. However, its specific effects in Cesarean myomectomy remain underexplored. Objective: This study aimed to evaluate the efficacy and safety of intravenous TXA in reducing blood loss during Cesarean myomectomy. Patients and methods: This double-blind, randomized controlled trial was performed in Aswan University Hospital. Pregnant women undergoing Cesarean myomectomy were randomly assigned to receive intravenous TXA or placebo before skin incision, 39 in each group. The primary end point was total intraoperative blood loss. Secondary outcomes assessed were blood transfusion requirement, hemoglobin and hematocrit levels difference, postpartum hemorrhage (PPH) rate and adverse events. Results: Intraoperative blood loss was significantly lower in the TXA group (medians 700 mL [IQR 101] vs 950 mL [IQR 150] in the placebo group, p < 0.001). Similarly, the use of red blood cell transfusion was less in the TXA group (median 0 units [IQR 1]) vs. the placebo group (median 2 units [IQR 2], p < 0.001). The TXA group had greater postoperative hemoglobin and hematocrit levels. The incidence of PPH was significantly lower in the TXA group (25.7%) than in the placebo group (51.4%, p = 0.027). No thromboembolic events or other significant adverse effects were observed. Conclusion: Intravenous TXA significantly reduced blood loss and transfusion requirements in women undergoing Cesarean myomectomy, with no increase in adverse events. TXA is a valuable adjunct in managing perioperative blood loss during this complex procedure.