The American College of Surgeons' Committee on Trauma's recent prehospital trauma life support recommendations against prehospital spine immobilization (PHSI) after penetrating trauma are based on a low incidence of unstable spine injuries after penetrating injuries. However, given the chronic and costly nature of devastating spine injuries, the cost-utility of PHSI is unclear. Our hypothesis was that the cost-utility of PHSI in penetrating trauma precludes routine use of this prevention strategy. A Markov model based cost-utility analysis was performed from a society perspective of a hypothetical cohort of 20-year-old males presenting with penetrating trauma and transported to a US hospital. The analysis compared PHSI with observation alone. The probabilities of spine injuries, costs (US 2010 dollars), and utility of the two groups were derived from published studies and public data. Incremental effectiveness was measured in quality-adjusted life-years. Subset analyses of isolated head and neck injuries as well as sensitivity analyses were performed to assess the strength of the recommendations. Only 0.2% of penetrating trauma produced unstable spine injury, and only 7.4% of the patients with unstable spine injury who underwent spine stabilization had neurologic improvement. The total lifetime per-patient cost was $930,446 for the PHSI group versus $929,883 for the nonimmobilization group, with no difference in overall quality-adjusted life-years. Subset analysis demonstrated that PHSI for patients with isolated head or neck injuries provided equivocal benefit over nonimmobilization. PHSI was not cost-effective for patients with torso or extremity penetrating trauma. Despite increased incidence of unstable spine injures produced by penetrating head or neck injuries, the cost-benefit of PHSI in these patients is equivocal, and further studies may be needed before omitting PHSI in patients with penetrating head and neck injuries. Economic and value-based evaluation, level II.