OBJECTIVE Gastrointestinal (GI) bleeding is a common medical emergency with significant morbidity and mortality. Many patients are coagulopathic, which may perpetuate bleeding. Remote damage control resuscitation, including early correction of coagulopathy and anemia, may benefit exsanguinating patients with GI bleeding. METHODS We conducted a retrospective review of patients with acute GI bleeding who received packed red blood cells (pRBC) and/or plasma during transportation to our institution between 2010 and 2014. A comparison group of patients who were not transfused en route was selected, and demographics, outcomes, and response to resuscitation were compared. RESULTS A total of 112 patients with GI bleeding received pRBC (82%, n = 92 pRBC, mean 1.7 ± 0.9 units), plasma (62%, n = 69, mean 1.7 ± 0.8 units) or both (44%, n = 49) en-route. The comparison group comprised 49 patients transported by helicopter who were not transfused en-route. Demographics, crystalloid resuscitation, transfusion prior to transfer, rate of intervention, ICU days, length of stay, and mortality were similar between groups. Patients transfused en route had a significant increase in hemoglobin from 8.3 ± 2.2 to 8.9 ± 2.1 (P = .03) and decrease in INR from 2.0 ± 1.0 to 1.6 ± 1.4 (P = .01), whereas those not transfused en route experienced stable hemoglobin (8.7 ± 2.8 to 9.4 ± 2.5; P = .21) and INR values (1.9 ± 1.0 to 1.6 ± 1.4; P = .32). Both groups had a significant improvement in hemodynamic parameters with resuscitation. CONCLUSIONS Prehospital damage control resuscitation with pRBC and/or plasma resulted in the improvement of hemodynamic instability, coagulopathy and anemia in patients with acute GI bleeding. Almost all patients required additional inpatient interventions and/or transfusions, suggesting that pre-hospital transfusion is being utilized for appropriately selected patients.