Abstract Children who survive severe traumatic brain injury (sTBI) live with profound impairments that alter their development and future possibilities. Worldwide, TBI is the leading cause of death and disability among children and adolescents. In the US, the annual incidence of pediatric TBI is greater than MS, HIV/AIDS, spinal cord injury, and breast cancer combined1. Although not strictly pediatric diseases, this comparison illustrates the magnitude and importance of the pediatric global health epidemic we are addressing. Our primary focus for scientific investigation is to conduct a high quality randomized controlled trial addressing a critical TBI management question: Does using a protocol with information from intracranial pressure (ICP) monitoring to direct treatment of children with sTBI improve outcomes vs an aggressive management protocol based on imaging and clinical examination alone? This follows on our adult ICP study2 which found no outcome differences and has occasioned re-thinking of treatment guidelines for sTBI patients >13. A separate study is essential because children are not simply small adults and some treatment approaches carry age-related additional risks. Thus, study findings will inform US and global clinical practice. This trial will be conducted in 7 Latin American pediatric ICUs where infrastructures and practice patterns are optimal for strong internal validity and resources represent trauma care in the developing world. The successful adolescent/adult BEST TRIP trial, which collected high-quality data in similar environments (cited > 900 times) underscores the feasibility of this approach. Specific Aim: In a Phase III randomized superiority trial in 428 children with sTBI from 7 Latin American pediatric trauma centers, test the effect on outcomes of management of sTBI guided by a protocol using information from ICP monitors vs. management using a protocol that uses imaging and clinical exams to guide treatment. Hypothesis #1: Children with severe TBI whose acute care treatment is managed using a protocol based on data from ICP monitoring will have significantly lower mortality and better quality of life and global outcome at 6 months post-trauma than those whose treatment is managed with a protocol based on imaging and clinical exam. The primary measure of functional recovery is the PedsQL at 6 months. A secondary measure is GOSE-Peds. Hypothesis #2: Incorporating ICP monitoring into sTBI patient care of will minimize secondary complications, decrease length of stay in ICU and decrease brain-specific treatments. Specific Aim: We will train personnel in centers new to research in how to conduct high-quality scientific studies, and will extend the training for the personnel with whom we have been working, solidifying previous capacity- building efforts, and initiating new efforts.