In the past 5 years, cerebral perfusion pressure (CPP) management has become the standard in the treatment of severe head injuries. Guidelines published in 2000 suggest that CPP should be at least 70 mmHg; however, there is still debate about the optimal CPP. The purpose of the present study was to evaluate the effectiveness of these three widely used therapies: (i) intracranial pressure (ICP) targeted; (ii) CPP-targeted with CPP >70 mmHg; and (iii) modified CPP-targeted (mCPP) therapy with CPP >60 mmHg. The clinical procedures, complications and outcomes of patients in the different groups were compared. Data, including patient age, sex, initial Glasgow Coma Scale, ICP, CPP, fluid status, amount of mannitol and vasopressor used, daily fluid intake and output, complications and clinical results, were collected from 213 patients with severe head injuries over a 12-year period. Patients were categorized into three groups (ICP, CPP, mCPP) according to the treatment protocol used. Retrospective data collection was performed by chart review. The mortality rate was 28.6%, 14.3% and 13.5% in the ICP, CPP, and mCPP groups, respectively. Highest intake/output ratio, amount of vasopressor used and pulmonary complications were seen in the CPP patients. The mCPP patients showed the best clinical outcome and lowest complication rate. Although CPP-targeted therapy is the most recommended therapeutic protocol, our data show that patients treated with modified CPP-target therapy with CPP >60 mmHg have better clinical outcomes and fewer complications.