Service members in theater or military training frequently are exposed to primary blast by explosive weaponry. Thus, blast-induced mTBI is the most common form of TBI, regarded as a ‘Signature Wound or Invisible Injury’ in recent military conflicts. This highly reproducible, open-field low-intensity blast (LIB) injury in mice, the “Missouri Blast” model, uses detonating 350 g of high-energy explosive Composition C-4 (C4). Open-field LIB with C4, set at 1-m above the ground, generates the initial Friedlander waveform with blast rise time on microsecond scale, and includes interactions from the primary blast shockwave reflection off the ground. Comprehensive physical characterization includes the measurements of peak overpressure, blast rise time, positive phase duration, impulse, and velocity of blast waves. High-speed videography is used to capture the dynamic blast events and to ensure the reproducibility of the experimental blast exposures, confirming the absence of visible impact / acceleration on the blast-exposed mice in prone position. This model is scalable and allows study of varying magnitudes of primary blast injuries by placing animals at different distances away from the center of the blast. Overall, this animal model will provide a platform to enhance the understanding of the pathogenesis of blast-induced brain injury and is critical for developing new prevention and treatment strategies against the risk for later neurodegeneration and cognitive impairments. A list of publications using this protocol can be found in the attached document.