Objective: To investigate whether the use of preoperative misoprostol can reduce blood loss during total abdominal hysterectomy (TAH).  Methods: In a randomized single-blind placebo-controlled trial at Ain Shams university maternity hospital, between May 2016 and June 2017, women (n = 118) undergoing TAH with or without bilateral salpingo-oophorectomy for symptomatic myomas were randomly allocated to receive either 400 μg of misoprostol or placebo 30 minutes before surgery. The primary outcome measure was postoperative drop in hemoglobin. The secondary outcomes were intraoperative blood loss, need for blood transfusion, and incidence of adverse effects. Results: The 2 groups were similar with regard to demographic and clinical characteristics. There was a significant reduction of blood loss during TAH after sublingual administration of misoprostol compared with placebo before surgery (355.1 mL vs 531.4 mL; P < 0.001). The mean postoperative hemoglobin concentration was higher (11.1g/dL vs 10.7 g/dL; P < 0.015) and the postoperative drop in hemoglobin was smaller (1.2 g/dL vs 1.8 g/dL; P < 0.001) in the misoprostol group than in the placebo group.  No significant adverse effects occurred in either group. Conclusion: The results showed that a single dose of misoprostol administered before abdominal hysterectomy resulted in a significant reduction of blood loss with minimal adverse effects.