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Background: The value of tranexamic acid (TA) treatment as bleeding prophylaxis in major uterine surgery is unclear., Objectives: To evaluate the antihemorrhagic effect of prophylactic TA treatment in major benign uterine surgery., Search Strategy: PubMed, Embase, Cochrane Library, and Web of Science were searched from 1980 to 2015 without language restriction using search terms related to major uterine surgery combined with TA., Selection Criteria: Randomized controlled trials comparing prophylactic TA with placebo or no intervention in women undergoing elective major benign uterine surgery., Data Collection and Analysis: Basic information and outcomes were collected and meta-analyses performed., Main Results: Sixteen trials were included, with five trials considered to have an overall low risk of bias. In cesarean delivery, TA significantly reduced intraoperative bleeding (mean -136 mL, 95% confidence interval [CI] -189 to -83), blood loss of more than 1000 mL (relative risk 0.38, 95% CI 0.18-0.81), and blood transfusion (relative risk 0.32, 95% CI 0.17-0.59). In abdominal myomectomy, TA also significantly reduced intraoperative bleeding (mean -251 mL, 95% CI -391 to -110)., Conclusions: Prophylactic TA treatment significantly reduced operative bleeding in women undergoing elective cesarean delivery or abdominal myomectomy. Additional randomized trials with low risk of bias are needed., (© 2016 International Federation of Gynecology and Obstetrics.)