BACKGROUND: The value of prehospital blood transfusion (PHBTx) in the management of severe trauma has not been established. This study aimed to evaluate the effect of PHBTx on mortality in combat casualties. METHODS: This is a retrospective cohort study of casualties admitted to the field hospital at Camp Bastion, Afghanistan, by the Medical Emergency Response Team from May 2006 to March 2011. Participants were divided into two consecutive cohorts by the introduction of PHBTx. Paired groups of patients were chosen by combining propensity score methodology with detailed matching of injury profile. Thus recipients of PHBTx were matched with nonrecipients who would have received it had it been available. RESULTS: A total of 1,592 patients were identified. Of the 1,153 patients to whom PHBTx was potentially available, 310 received it (26.9%). The rate of severe injury (Injury Severity Score [ISS] > 15) rose from 28% before PHBTx was available to 43% thereafter (p < 0.001). Mortality in the latter group was higher (14% vs. 10%, p = 0.013) but not in the severely injured patients (32% vs. 28%, p = 0.343). Ninety-seven patients were paired. The mortality of matched patients who received PHBTx, compared with those with similar injury patterns who did not, was less than half (8.2% vs. 19.6%, p < 0.001). However, matched recipients had more prehospital interventions, reached hospital more quickly, and had lower heart rate at admission (all p < 0.05). Matched recipients received more red blood cells within 24 hours (median, 4 U; interquartile range [IQR], 2-10 U) than nonrecipients (median 0 U; IQR, 0-3.5 U) and more fresh frozen plasma (median, 2 U; IQR, 2-9 U vs. median, 0 U; IQR, 0-1 U) (both p < 0.001). CONCLUSION: An aggressive approach to damage control resuscitation including the use of PHBTx was associated with a large improvement in mortality. However, because of confounders resulting from changes in practice, the isolated contribution of PHBTx cannot be determined from this study. LEVEL OF EVIDENCE: Therapeutic study, level IV. Copyright © 2014 Lippincott Williams & Wilkins.