OBJECTIVE： To evaluate the efficacy and safety of progesterone in the treatment of acute traumatic brain injury systematically， and to provide reference for clinical use. METHODS： Retrieved from Cochrane library， ClinicalTrials， Web of Science， PubMed， Embase， CBM， CNKI and Wanfang database， randomized controlled trial （RCTs） about progesterone （trial group） versus placebo or blank control （control group） in the treatment of acute traumatic brain injury were collected. After literature screening， data extraction and quality evaluation by risk bias evalution tool of Cochrane systematic evaluator manual 5.1.0， Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS： A total of 10 RCTs were included， involving 2 652 patients. Results of Meta-analysis showed that there was no statistical significance in mortality[RR＝0.77，95％CI（0.56，1.07），P＝0.12]， the incidence of septicemia [RR＝1.11，95％CI（0.77，1.60），P＝0.59] or elevated liver enzymes[RR＝1.30，95％CI（0.68，2.50），P＝0.43]. The number of patients with favorable neurological outcome[RR＝1.23，95％CI（1.05，1.43），P＝0.008] in trial group was significantly more than control group. Results of subgroup analysis of mortality showed that there was no statistical significance in the mortality of patient’s GCS≤8 [RR＝0.79，95％CI（0.57，1.10），P＝0.16]， that of patient’s GCS≤12[RR＝0.69，95％CI（0.23，2.10），P＝0.52] or that of patient’s GCS ranging from 9 to 12 [RR＝0.78，95％CI（0.26，2.35），P＝0.65] between 2 groups. Results of subgroup analysis of neurological outcome showed that there was no statistical significance in the number of favorable neurological outcome of patient’s GCS≤8 [RR＝1.18， 95％CI（0.98，1.43），P＝0.09]， the number of favorable outcome of patient’s GCS≤12[RR＝1.15，95％CI（0.87，1.51），P＝0.32] and the number of favorable neurological outcome of patient’s GCS ranging from 9 to 12[RR＝2.07，95％CI（0.24，17.71），P＝0.51]. CONCLUSIONS： Progesterone can improve the prognosis of neurological function in patients with acute traumatic brain injury with good safety but cannot reduce mortality.