This symposium brings together international experts and policy-makers to discuss scientific and political strategies to improve research outcomes in the field of traumatic brain injury. Brain trauma is a major, global health problem, with no proven therapies. Therapy development for traumatic brain injury is challenging because of the heterogeneity of the pathophysiology and because of the high variability in diagnostic and treatment options across the world. This variability complicates the interpretation of clinical trial results. Comparative effectiveness research has recently emerged as a very effective tool to discriminate among clinical interventions by providing evidence on their effectiveness, benefits, and harms. The evidence is generated from comparative research studies that determine what works best for which patients in real-world settings. This symposium will discuss the current state of play, unmet needs, and future directions in traumatic brain injury research, including how comparative effectiveness research could improve clinical guidelines and treatments in this field. Last but not least, this event will explore the opportunities and benefits for conducting effective traumatic brain injury research across borders -- in particular, how the European Commission and the National Institutes for Health could work in synergy to harmonize standards, increase effectiveness of clinical trials, and, ultimately, improve health outcomes around the world.