Tranexamic acid (TXA) is widely used to manage acute brain injuries, including subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury. Despite its common usage, there is limited evidence on its safety in these conditions. We aimed to evaluate the impact of TXA on mortality and thromboembolic events in patients with acute brain injury. A systematic search of MEDLINE/PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted from inception to May 2024. We included randomized controlled trials (RCTs) comparing TXA with placebo in patients aged 15 years or older with confirmed acute brain injury. Two reviewers independently assessed study quality using the revised Cochrane Risk of Bias tool and extracted data on patient demographics, intervention details, and outcomes, including mortality, thromboembolic events, and seizures. Meta-analyses were performed using random effects models. Twenty-five RCTs with 16,677 participants (8584 TXA, 8093 control) were included. The relative risk (RR) for overall mortality was 0.96 (95% confidence interval (CI) 0.91–1.03, p = 0.2433), indicating a nonsignificant difference between the groups, with no substantial heterogeneity (I2 = 0% [0–45%]). Additionally, no significant differences were observed in 30-, 90-, or 180-day mortality. The RR for total thromboembolic events was 1.11 (95% CI 0.97–1.28, p = 0.1236), indicating a nonsignificant difference between the groups, with low heterogeneity (I2 = 15% [0–51%]). Similarly, no significant differences were observed in the incidences of deep vein thrombosis or pulmonary embolism, ischemic stroke or transient ischemic attack, acute coronary syndrome or myocardial infarction, or seizures. However, the administration of TXA for more than 1 day was associated with a significant increase in thromboembolic events (RR 1.22, 95% CI 1.03–1.44). Administering TXA beyond 8 h of injury was also associated with a significant increase in thromboembolic events (RR 1.16, 95% CI 1.02–1.33). TXA administration does not significantly affect overall mortality or increase the risk of thromboembolic events in patients with acute brain injuries. However, prolonged use or delayed administration may be associated with an increased risk of thromboembolic events.