Abstract Background: Many animal studies have delineated the neuroprotective effect of magnesium (Mg) in traumatic brain injuries. It protects neurons from ischemic injuries and supports neuronal survival following TBI. Aim of Study: The aim of this study is to assess the role of Mg as a neuroprotective in patients with moderate and severe traumatic brain injury. Patients and Methods: This is a double blind placebo con-trolled study. Sixty victims of traumatic brain injury (TBI), moderate and severe were randomly allocated into one of two equal groups; Mg sulphate (Group A), or normal saline as pla-cebo (Group B) from April to August 2019 in one of neuro-surgical ICUs in the following centers; Kasr El-Aini Hospitals, Beni-Suef University Hospital or Beni-Suef General Hospital. All patients had received the standard management as per brain trauma foundation guidelines, including surgical intervention when deemed necessary. Outcome was assessed using Glasgow outcome scale (GOS) and mortality rate after two months. Results: From April to August 2019, sixty victims of TBI has been enrolled. Patients have been admitted to neurosurgical intensive care unit. The mean age was 33.9 years. Sex distri-bution showed an evident male predominance in both groups (83.3%). After 2 months, favorable outcome (good recovery and moderate disability) was achieved in 18 patients in group A, and 19 patients in group B, the difference was statistically insignificant. There were 22 mortality that represented 36.6% of the whole study group, 12 cases in group A, and 10 cases in group B. Conclusion: The study did not identify a significant bene-ficial effect in reducing mortality in traumatic brain injury after administration of Mgso4; however, it suggested that magnesi-um sulfate shows a tendency to improve the outcome after 2 months as long as GCS was better on admission. Trial registration: ClinicalTrials.gov NCT04646876. Conflict of interest statement: The authors declare that the research was conducted in absence of any commercial or finan-cial relationships that could be construed as a potential conflict of interest.