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Clinical practice guidelines (CPGs) are used to keep providers up-to-date with the most recent literature and to guide in decision making. Adherence is typically improved although many have a muted impact. In March 2006, the US Army issued a damage control resuscitation CPG, encouraging 1:1 plasma:red blood cell (RBC) transfusions and limiting crystalloid use. The objective of this study was to determine whether the CPG was associated with a change in the transfusion practices in combat-wounded patients.All US service members injured in Operation Iraqi Freedom/Operation Enduring Freedom who received massive transfusions (MTs; ≥10 RBC in 24 hours) were queried from the US Army Institute of Surgical Research transfusion database. Whole blood, when used, was counted as 1 unit of RBC, fresh frozen plasma (FFP), and platelet. Subjects were divided into pre- and post-CPG cohorts. Primary outcomes were ratios of FFP:RBC and crystalloid use.A total of 777 MT patients were identified. The cohorts were similar in age (25 years ± 6 years vs. 25 years ± 6 years; p = ns) and injury severity scale score (24 ± 12 vs. 25 ± 12; p = ns). The post-CPG cohort was warmer (96.5°F ± 7.8°F vs. 98.2°F ± 1.9°F; p < 0.05) and was transfused more RBC, platelets, and plasma but received less crystalloid (17 units ± 12 units vs. 19 units ± 11 units, 1 unit ± 2 units vs. 2 units ± 3 units, 8 units ± 8 units vs. 14 units ± 11 units, 14 L ± 14 L vs. 9 L ± 13 L, respectively; p < 0.05). The post-CPG cohort also received a higher ratio transfusion (0.5 ± 0.31 vs. 0.8 ± 0.31; p < 0.05) representing a change in practice. Overall mortality was not different between the two groups (24 vs. 19%; p = 0.115).MT patients are now receiving a higher FFP:RBC ratio and less crystalloid after implementation of the CPG. Additionally, patients are now presenting normothermic and have higher hemoglobin levels. All of these changes are consistent with the principles of damage control resuscitation. Changes in practice were associated with implementation of the CPG, maturity of the battlefield, and increased availability of products.