BACKGROUND: A skull defect is inevitable after decompression treatment for traumatic brain injury. Titanium mesh as the most recognized skull repair material has good biocompatibility and has been widely used in clinical practice. However, the timing for skull repair after brain injury is still in dispute.OBJECTIVE: To compare the changes of brain perfusion and the recovery of neurological function in patients with skull defects before and after early and late-stage titanium mesh repair based on CT perfusion technique.METHODS: This was a single-center, prospective, observational clinical trial that was completed at the Taihe Hospital,Hubei University of Medicine in Hubei Province, China. Eighty-six patients with craniocerebral injury who had undergone decompression with removal of bone flap from January 2013 to January 2016 were recruited and subjected to skull repair using titanium mesh. All the patients were randomized into two groups: test group (n=40) with early skull repair within 1-3 months after decompression and control group (n=46) with late-stage skull repair within 6-12 months after decompression. CT perfusion technology was used to observe changes of brain perfusion at 3 days operatively and at 10 days postoperatively. The Barthel index was evaluated at 30 days postoperatively. The trial was registered with ClinicalTrial.gov (identifier: NCT03222297) on July 12th, 2017. The study protocol was approved by the Ethics Committee of Taihe Hospital with the approval No. 2012 (08), and performed in accordance with the Declaration of Helsinki,formulated by the World Health Organization and the hospital's ethical requirements for human research. All the patients and their families were voluntary to participate in the trial, were fully informed of the trial process, and then signed the informed consent prior to the initialization of the trial.RESULTS AND CONCLUSION: The postoperative cerebral blood volume and cerebral blood flow at the parietal cortex on the side of skull defect and at the cortex in the defect region were significantly higher in the two group than the baseline (P < 0.05), while the time to peak was lower than the baseline (P < 0.05). Compared with the control group,significantly higher cerebral blood volume and cerebral blood flow as well as shorter time to peak were observed in the test group (P < 0.05). The Barthel index of the test group was also significantly higher than that of the control group at 30 days postoepratively (P < 0.05). Overall, early skull repair with titanium mesh is helpful to improve the cerebral blood perfusion at the affected side and the recovery of neurological function. In addition, CT perfusion technology is a safe and effective method to monitor hemodynamic changes in the brain.