Background: In the era of evidence-based health care, protocol of intervention in traumatic brain injury (TBI) cases help decide more easily and safely about patients and prevent unnecessary transfer of patients to other centers. Objectives: The objective of this study is to provide protocol-based intervention and evaluate the epidemiological, clinical characteristics of TBI cases. Methods: This prospective study was conducted on 704 patients who were suspected of TBI at the Department of Neurosurgery, Narayana Medical College and Hospital, followed by protocol-based intervention assessed and reassessed repeatedly. Results: Overall, TBI involved 569 (80.82%) adults in the productive age groups (21–60 years); among males 81.47%. Among males, highest (23.15%) cases were in the age group of 31–40 years while in females, majority (27.04%) was among 41–50 years. Road traffic accidents were the most common (54.12%) mechanism of injury followed by fall (21.31%) and two-wheelers (15.20%). More than half sustained mild TBI (51.42%) while 26.28% moderate TBI and 22.30% severe TBI; among males, severe TBI victims 102 (18.82%) were in the productive age group. Loss of consciousness was almost a universal and significant observation (95.45%); vomiting was next common finding (76.42%). Bleeding from the ear-nose-throat (ENT) region was more in males (33.58%) than females (20.75%). Glasgow coma scale was significantly related with loss of consciousness (91.08%), vomiting (63.06%), and ENT bleeding (44.59%) in severe, moderate, and mild injuries. Conclusion: A rational clinical acumen with judicious use of diagnostic protocol leads to better management of TBI without unnecessary imaging and thus reduce total health-care costs.