Progesterone has been shown to have neuroprotective effects in multiple animal models of brain injury, whereas the efficacy and safety in patients with traumatic brain injury (TBI) remains contentious. Here, a total of seven randomized controlled trials (RCTs) with 2492 participants were included to perform this meta-analysis. Compared with placebo, there was no significant decrease to be found in the rate of death or vegetative state for patients with acute TBI (RR = 0.88, 95%CI = 0.70, 1.09, p = 0.24). Furthermore, progesterone was not associated with good recovery in comparison with placebo (RR = 1.00, 95%CI = 0.88, 1.14, p = 0.95). Together, our study suggested that progesterone did not improve outcomes over placebo in the treatment of acute TBI.