OBJECTIVE To elucidate the effectiveness of brain tissue oxygenation (PbtO2) plus intracranial pressure (ICP) monitoring and targeted therapy in patients of severe traumatic brain injury (TBI). METHODS A total of 46 patients with severe TBI (Glasgow coma scale, GCS scale ≤ 8) admitted at Jiangyin People's Hospital from June 2009 to June 2012 were divided randomly into 2 groups and evaluated prospectively.Patients undergoing ICP plus PbtO2 monitoring were compared with controls with ICP monitoring alone.Therapies of both patient groups were attempted to maintain an ICP < 20 mm Hg and a cerebral perfusion pressure (CPP) ≥ 60 mm Hg.Among those with PbtO2 monitoring, oxygenation was maintained at a level of ≥ 20 mm Hg.The scores of Glasgow outcome scale (GOS) were compared between two groups at Month 6 post-injury. RESULTS The mean daily ICP and CPP levels were similar in each group.The mortality rate was 21.7% in patients with ICP monitoring alone and the favorable outcome rate was 47.8%.However, those receiving combined management had a significantly reduced mortality rate of 8.7% and good outcome rate of 65.2% (P < 0.05). CONCLUSIONS The combined use of both ICP and PbtO2 may be associated with reduced mortality and improved outcome in patients with severe TBI.