Optimal hemostatic resuscitation in pediatric trauma is not well defined. To assess the association of prehospital blood transfusion (PHT) with outcomes in injured children. This retrospective cohort study of the Pennsylvania Trauma Systems Foundation database included children aged 0 to 17 years old who received a PHT or emergency department blood transfusion (EDT) from January 2009 and December 2019. Interfacility transfers and isolated burn mechanism were excluded. Analysis took place between November 2022 and January 2023. Receipt of a blood product transfusion in the prehospital setting compared with the emergency department. The primary outcome was 24-hour mortality. A 3:1 propensity score match was developed balancing for age, injury mechanism, shock index, and prehospital Glasgow Comma Scale score. A mixed-effects logistic regression was performed in the matched cohort further accounting for patient sex, Injury Severity Score, insurance status, and potential center-level heterogeneity. Secondary outcomes included in-hospital mortality and complications. Of 559 children included, 70 (13%) received prehospital transfusions. In the unmatched cohort, the PHT and EDT groups had comparable age (median IQR, 47 9-16 vs 14 9-17 years), sex (46 66% vs 337 69% were male), and insurance status (42 60% vs 245 50%). The PHT group had higher rates of shock (39 55% vs 204 42%) and blunt trauma mechanism (57 81% vs 277 57%) and lower median (IQR) Injury Severity Score (14 5-29 vs 25 16-36). Propensity matching resulted in a weighted cohort of 207 children, including 68 of 70 recipients of PHT, and produced well-balanced groups. Both 24-hour (11 16% vs 38 27%) and in-hospital mortality (14 21% vs 44 32%) were lower in the PHT cohort compared with the EDT cohort, respectively; there was no difference in in-hospital complications. Mixed-effects logistic regression in the postmatched group adjusting for the confounders listed above found PHT was associated with a significant reduction in 24-hour (adjusted odds ratio, 0.46; 95% CI, 0.23-0.91) and in-hospital mortality (adjusted odds ratio, 0.51; 95% CI, 0.27-0.97) compared with EDT. The number needed to transfuse in the prehospital setting to save 1 child's life was 5 (95% CI, 3-10). In this study, prehospital transfusion was associated with lower rates of mortality compared with transfusion on arrival to the emergency department, suggesting bleeding pediatric patients may benefit from early hemostatic resuscitation. Further prospective studies are warranted. Although the logistics of prehospital blood product programs are complex, strategies to shift hemostatic resuscitation toward the immediate postinjury period should be pursued.