Aim:This study evaluated the safety and efficacy of the hybrid operating room (HOR) approach in the management of severe traumatic brain injury (sTBI) using Xper-computed tomography (CT)-guided imaging and neurointerventional techniques.Material and Methods:A retrospective analysis was conducted on 154 patients with TBI treated surgically between February 2020 and December 2023. Among these, 26 patients with sTBI were managed in an HOR equipped with an Allura Xper FD 20® system. Intraoperative interventions included Xper-CT confirmation, real-time imaging-guided hematoma aspiration or catheter placement, and combined neurointerventional procedures. Clinical outcomes were assessed using the Glasgow Outcome Scale-Extended (GOS-E) at 6 months, and procedural morbidity and mortality rates were documented.Results:The 26 patients with sTBI had a mean age of 45.3±12.0 years, with 60.4% being male. Xper-CT was used in all cases (mean: 1.7 scans/patient) for confirmation and in 11 cases (42.3%) for real-time guidance, enabling precise interventions such as parenchymal hematoma aspiration (30.8%) and external ventricular drainage (11.5%). Vascular injuries were managed with N-butyl cyanoacrylate glue or polyvinyl alcohol particle embolization (15.4%) and endovascular coiling for pseudoaneurysms (11.5%), with intraoperative angiography performed in 7.7% of cases. No HOR-related complications or reoperations were noted. Favorable outcomes (GOS-E≥4) were observed in 42.3% of patients at 6 months, whereas the 28-day mortality rate was 19.2%, primarily owing to initial trauma (n=3) and pneumonia or sepsis (n=2).Conclusion:The HOR approach represents a significant advancement in the management of sTBI and potentially improves the overall quality of emergency neurosurgical care.