BACKGROUND: Pediatric massive blood transfusions occur widely at hospitals across the nation; however, there are limited data on pediatric massive transfusion protocols (MTPs) and their impact. We present a pediatric MTP and examine its impact on morbidity and mortality as well as identify factors that may prompt protocol initiation. METHODS: Using a prospective cohort, we collected data on all pediatric patients who required un-cross-matched blood from January 1, 2009, through January 1, 2011. This captured patients who received blood products according to the protocol as well as patients who were massively transfused at physician discretion. Outcomes between groups were compared. RESULTS: A total of 55 patients received un-cross-matched blood, with 22 patients in the MTP group and 33 patients receiving blood at physician discretion (non-MTP group). Mortality was not significantly different between groups. Injury Severity Score for the MTP group was 42 versus 25 for the non-MTP group (p ≤ 0.01). Thromboembolic complications occurred more exclusively in the non-MTP group (p ≤ 0.04). Coagulopathy, evidenced by partial thromboplastin time (PTT) greater than 36, was associated with initiation of the MTP. CONCLUSION: MTPs have been widely adopted by hospitals to minimize the coagulopathy associated with hemorrhage. Blood transfusion via MTP was associated with fewer thromboembolic events. Coagulopathy was associated with initiation of the MTP. These results support the institution of pediatric MTPs and suggest a need for further research on the protective relationship between MTP and thromboembolic events and on identifying objective factors associated with MTP initiation. LEVEL OF EVIDENCE: Therapeutic study, level IV. © 2012 Lippincott Williams & Wilkins.