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Spine immobilization in trauma has remained an integral part of most emergency medical services protocols despite a lack of evidence for efficacy and concern for associated complications, especially in penetrating trauma patients. We reviewed the published evidence on the topic of prehospital spine immobilization or spinal motion restriction in adult patients with penetrating trauma to structure a practice management guideline.We conducted a Cochrane style systematic review and meta-analysis and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology to construct recommendations. Qualitative and quantitative analyses were used to evaluate the literature on the critical outcomes of mortality, neurologic deficit, and potentially reversible neurologic deficit.A total of 24 studies met inclusion criteria, with qualitative review conducted for all studies. We used five studies for the quantitative review (meta-analysis). No study showed benefit to spine immobilization with regard to mortality and neurologic injury, even for patients with direct neck injury. Increased mortality was associated with spine immobilization, with risk ratio [RR], 2.4 (confidence interval [CI], 1.07–5.41). The rate of neurologic injury or potentially reversible injury was very low, ranging from 0.002 to 0.076 and 0.00034 to 0.055, with no statistically significant difference for neurologic deficit or potentially reversible deficit, RR, 4.16 (CI, 0.56–30.89), and RR, 1.19 (CI, 0.83–1.70), although the point estimates favored no immobilization.Spine immobilization in penetrating trauma is associated with increased mortality and has not been shown to have a beneficial effect on mitigating neurologic deficits, even potentially reversible neurologic deficits. We recommend that spine immobilization not be used routinely for adult patients with penetrating trauma.Systematic review with meta-analysis study, level III.