Background: Traumatic brain injury (TBI) complicated by intracranial hemorrhage is a major contributor to morbidity and mortality among trauma patients. Tranexamic acid, an antifibrinolytic agent widely used to reduce surgical blood loss, has been proposed as a potential intervention to limit hemorrhage progression and improve clinical outcomes in patients with acute TBI. Objective: To evaluate the efficacy and safety of tranexamic acid in patients with acute traumatic brain injury. Methods: A systematic review of randomized controlled trials was conducted. An advanced search of PubMed was performed in August 2025, supplemented by searches of the Cochrane Collaboration database, Google Scholar©, and clinical trial registries. Eligible studies included prospective randomized controlled trials evaluating tranexamic acid in patients with traumatic brain injury. Data were independently extracted from included studies. Outcomes assessed included mortality, adverse events, requirement for neurosurgical intervention or blood transfusion, volume of blood transfused, intracranial hemorrhage growth and expansion, ischemic brain lesions, and functional disability at discharge. The quality of evidence was assessed using the GRADE approach. Results: Five randomized controlled trials met the inclusion criteria, comprising a total of 13477 patients. The pooled analysis demonstrated that tranexamic acid significantly reduced the risk of intracranial hemorrhage growth by 52% (RR 0.48, 95% CI 0.61–0.98; p = 0.03). Tranexamic acid also significantly reduced the risk of unfavorable functional status at discharge by 24% (RR 0.76, 95% CI 0.61–0.93; p = 0.009). No significant effect of tranexamic acid was observed on mortality, need for neurosurgical intervention, or total hemorrhage expansion. No increase in risk of adverse events was reported. Conclusion: Tranexamic acid administered within eight hours of injury safely reduces intracranial hemorrhage progression and unfavorable functional outcomes at discharge, thereby limiting morbidity in patients with traumatic brain injury without increasing the risk of adverse events. While these findings suggest a beneficial role for Tranexamic Acid in reducing morbidity, uncertainty regarding its impact on mortality remains, highlighting the need for further well-designed randomized trials

Traumatic brain injury, Tranexamic acid, Intracranial hemorrhage, Functional outcome