In the past 5 years cerebral perfusion pressure (CPP) management has become mainstream in the treatment of severe head injuries. The American Association of Neurological Surgeons guidelines (2000) suggest that CPP should be maintained at least 70 mmHg; however, there is still debate about optimal CPP level. The purpose of this study is to evaluate the effectiveness of three widely used therapies: intracranial pressure (ICP)-targeted therapy, CPP-targeted therapy with CPP > 70 mmHg, and modified CPP-targeted therapy with CPP > 60 mmHg. The clinical procedures, complications, and patient outcomes are compared. Data including patient age, sex, initial Glasgow Coma Score (GCS), ICP, CPP, fluid status, amount of mannitol and vasopressor used, daily 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, modified CPP [mCPP]) according to treatment protocol used. Retrospective data collection was by chart review. The mortality rate was 28.6%, 14.3%, and 13.5% in groups ICP, CPP, and mCPP, respectively. Highest intake/output ratio, amount of vasopressor used, and pulmonary complication rates were seen in group CPP patients. Group mCPP patients showed the best clinical outcome and lowest complication rate. Though CPP-targeted therapy is the most recommended therapeutic protocol, our data showed that the outcome is as good in the mCPP-targeted group with CPP > 60 mmHg as in the CPP-targeted group, but complications are fewer in the mCPP group.