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There have been no large cohort studies examining the wounding patterns and injury mechanisms in Iraq and Afghanistan from 2005 to 2009. This investigation sought to characterize the incidence and epidemiology of combat-related injuries for this period.Using the Joint Theater Trauma Registry, a detailed description of the combat casualty care statistics, distribution of wounds, and injury mechanisms sustained by all US service members for wounds (DRG International Classification of Diseases—9th Rev. codes 800–960) during the Iraq and Afghanistan Wars from 2005 to 2009 was performed.Among the 1,992,232 military service members who were deployed, there were 29,624 distinct combat wounds in 7,877 combat casualties. The mean age of the combat casualty cohort was 26.0 years old. The combat casualties were predominantly male (98·8%), Army (77·5%), and junior enlisted (59·0%). The distribution of combat wounds was as follows: head/neck, 28·1%; thorax, 9·9%; abdomen, 10·1%; and extremities, 51·9%. Explosive injury mechanisms accounted for 74·4% of all combat casualties, which was significantly higher than those caused by gunshot wounds (19·9%) (p < 0.0001). From 2005 to 2007, explosive mechanisms of injury were significantly more common in Iraq than in Afghanistan (p < 0.001). The percentage of explosive mechanisms increased significantly in Afghanistan between the years 2007 (59·5%) and 2008 (73·6%) (p < 0.0003).The wounding patterns observed in Iraq and Afghanistan from 2005 to 2009 differ from previous conflicts. Explosive mechanisms accounted for 74·4% of combat casualties, which is a higher percentage than in previous US conflicts. A progressive increase in the use of explosive mechanisms in Afghanistan, eventually equaling that in Iraq, was observed during the study period. (J Trauma Acute Care Surg. 2012;73: 3–12. Copyright © 2012 by Lippincott Williams & Wilkins)Epidemiological study, level II.