Clinical trials for traumatic brain injury (TBI) have faced significant challenges due to the complexity of the condition and the lack of effective therapies. Despite promising preclinical data, many trials have failed to demonstrate significant improvements in outcomes. The National Institute of Neurological Disorders and Stroke (NINDS) organized a workshop to address these issues, bringing together experts from clinical, research, and pharmaceutical backgrounds. The workshop highlighted key recommendations for future trials, including identifying specific mechanisms of cellular injury, focusing on appropriate patient subgroups, standardizing clinical management, choosing appropriate outcome measures, and ensuring adequate pharmacokinetic data. The workshop also emphasized the importance of proper trial design, including the use of surrogate endpoints and the need for large, well-controlled studies. The discussion covered various pharmacological treatments, including glutamate antagonists, steroids, and free radical scavengers, with mixed results. The importance of centralizing CT scan assessments and ensuring protocol adherence was also emphasized. The workshop concluded that future trials should focus on specific mechanisms of injury, use appropriate outcome measures, and ensure adequate pharmacokinetic data to improve the chances of success. The lessons learned from previous trials underscore the need for careful planning and execution in future TBI research.Clinical trials for traumatic brain injury (TBI) have faced significant challenges due to the complexity of the condition and the lack of effective therapies. Despite promising preclinical data, many trials have failed to demonstrate significant improvements in outcomes. The National Institute of Neurological Disorders and Stroke (NINDS) organized a workshop to address these issues, bringing together experts from clinical, research, and pharmaceutical backgrounds. The workshop highlighted key recommendations for future trials, including identifying specific mechanisms of cellular injury, focusing on appropriate patient subgroups, standardizing clinical management, choosing appropriate outcome measures, and ensuring adequate pharmacokinetic data. The workshop also emphasized the importance of proper trial design, including the use of surrogate endpoints and the need for large, well-controlled studies. The discussion covered various pharmacological treatments, including glutamate antagonists, steroids, and free radical scavengers, with mixed results. The importance of centralizing CT scan assessments and ensuring protocol adherence was also emphasized. The workshop concluded that future trials should focus on specific mechanisms of injury, use appropriate outcome measures, and ensure adequate pharmacokinetic data to improve the chances of success. The lessons learned from previous trials underscore the need for careful planning and execution in future TBI research.