Aim:Traumatic brain injury (TBI) is a severe disease with very high mortality, and most TBI patients are young adults. In the present study, we aimed to explore whether the combination regimen of dexmedetomidine (Dex) and butorphanol (But) could benefit patients with TBI.Material and Methods:A total of 208 TBI patients admitted from February 2018 to January 2020 were randomly divided into four groups as follows: control group (A), Dex group (B), But group (C), and combination of Dex and But group (D). Statistical analysis was performed to assess the changes in vital signs, oxygen saturation, serum neuroendocrine data, pain, and agitation scores.Results:The statistical data of vital signs and blood oxygen saturation of the four groups were compared, and the differences between group A and group D were statistically significant (P<0.05), indicating that a combination of sedative and analgesic agents at low doses could improve the vital signs of TBI patients, and the safety was relatively good. The scores of pain and agitation in the combination group were significantly improved on days 3 and 5, suggesting that the combination group was better compared with the control group.Conclusion:The combination of Dex and But was more suitable for the treatment of vital signs. Compared with the individual treatment groups, the patients in the combination group had a rapid improvement. Collectively, the combination of Dex and But could significantly benefit the prognosis of TBI.