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Context:   Seventy-seven percent of musculoskeletal injuries sustained by United States Army Special Forces Operators are preventable. Identification of predictive characteristics will promote the development of screening methods to augment injury-prevention programs., Objective:   To determine physical and performance characteristics that predict musculoskeletal injuries., Setting:   Clinical laboratory., Patients or Other Participants:   A total of 95 Operators (age = 32.7 ± 5.1 years, height = 179.8 ± 6.9 cm, mass = 89.9 ± 12.7 kg)., Main Outcome Measure(s):   Laboratory testing consisted of body composition, aerobic and anaerobic capacity, upper and lower body strength and flexibility, balance, and biomechanical evaluation. Injury data were captured for 12 months after laboratory testing. Injury frequencies, cross-tabulations, and relative risks (RRs) were calculated to evaluate the relationships between physical characteristics and injury proportions. Between-groups differences (injured versus uninjured) were assessed using appropriate t tests or Mann-Whitney U tests., Results:   Less shoulder-retraction strength (RR = 1.741 [95% confidence interval = 1.003, 3.021]), knee-extension strength (RR = 2.029 [95% confidence interval = 1.011, 4.075]), and a smaller trunk extension : flexion ratio (RR = 0.533 [95% confidence interval = 0.341, 0.831]) were significant risk factors for injury. Group comparisons showed less trunk strength (extension: P = .036, flexion: P = .048) and smaller right vertical ground reaction forces during landing ( P = .025) in injured Operators. Knee strength, aerobic capacity, and body mass index were less in the subgroup of spine-injured versus uninjured Operators ( P values = .013-.036)., Conclusions:   Knee-extension and shoulder-retraction strength were risk factors for musculoskeletal injury in Operators. Less trunk-flexion and -extension strength, higher body mass index, lower aerobic capacity, and increased ground reaction forces during landing were characteristics that may also contribute to musculoskeletal injury. Having 2 or more risk factors resulted in a greater injury proportion (χ 2 = 13.512, P = .015); however, more research is needed. Athletic trainers working in the military or similar high-demand settings can use these data to augment screening and injury-prevention protocols.