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.