Object. The authors sought to compare cerebral perfusion pressure (CPP)- with intracranial pressure (ICP)-targeted therapy in children with severe traumatic brain injury (TBI). Methods. A randomized controlled trial was developed to assess CPP and ICP therapies in 17 children (range 15 months-15 years of age) with poststabilization Glasgow Coma Scale (GCS) scores of less than or equal to 8 who were admitted to a pediatric intensive care unit at a Level I trauma center. Goals in the ICP group were to maintain ICP lower than 20 mm Hg and CPP higher than 50 mm Hg. In the CPP group, goals were to maintain CPP higher than 70 mm Hg for patients at least 2 years old and higher than 60 mm Hg for patients younger than 2 years of age. The study outcomes were death or functional outcome at 1 year postinjury. The median GCS scores in the CPP group (12 patients) and the ICP group (five patients) were 6 and 7, respectively. In the CPP group, two patients died, one was lost to follow up, four were unimpaired, and five had mild impairment. In the ICP group, all patients survived; one was lost to follow up, two had mild impairment, and two had hemiparesis and moderate impairment. There were four unimpaired survivors in the CPP arm compared with none in the ICP arm (p = 0.08). Conclusions. The CPP method appears to be safe, although this feasibility study does not establish that the CPP therapy is superior to ICP therapy.