Background:To evaluate the efficacy and side-effects of cyclosporine-A (CsA) in improvement of consciousness and cognitive dysfunction of patients with diffuse axonal injury (DAI) after traumatic brainMaterials and Methods:This study is designed as a randomized double-blind placebo-controlled with 100 patients suffered from DAI. CsA was administered to the intervention group (n = 50) as 5 mg/kg/24 h via 250 ml dextrose water (DW) 5% solution (DW 5%) during the first 8 h after trauma. The control group (n = 50) received only DW 5% in the same course. The presenting Glasgow coma scale in addition to the Glasgow outcome scale-extended (GOS-E) and mini-mental state examination (MMSE) in the 3rd and 6th months after trauma were documented. The serum values for complete blood count (CBC), blood urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were checked to assess for complications.Results:Most patients in both groups had type II DAI (46%). There was no significant difference between groups in the GOS-E scores after 3 and 6 months. All participants were in moderate or severe classes of MMSE with no statistically significant difference. Except for the higher BUN level in the cyclosporine treated group, 48 h after admission (P = 0.012), the difference in the level of Cr, AST, ALT, and ALP was not significant and all were in the normal range. The CBC results showed only significant difference for White Blood Cell (WBC) count at 12 h (P = 0.000).Conclusion:The administration of CsA is not effective in the improvement of consciousness and cognitive function. However, it brings about no adverse effects.