Objective: To audit the impact upon mortality of a massive bleeding management protocol (MBP) implemented in our center since 2007. Design: A retrospective, single-center study was carried out. Patients transfused after MBP implementation (2007-2012, Group 2) were compared with a historical cohort (2005-2006, Group 1). Background: Massive bleeding is associated to high mortality rates. Available MBPs are designed for trauma patients, whereas specific recommendations in the medical/surgical settings are scarce. Patients: After excluding patients who died shortly (<6 h) after MBP activation (n=20), a total of 304 were included in the data analysis (68% males, 87% surgical). Interventions: Our MBP featured goal-directed transfusion with early use of adjuvant hemostatic medications. Variables of interest: Primary endpoints were 24-h and 30-day mortality. Fresh frozen plasma to-red blood cells (FFP:RBC) and platelet-to-RBC (PLT:RBC) transfusion ratios, time to first FFP unit and the proactive MBP triggering rate were secondary endpoints. Results: After MBP implementation (Group 2; n=222), RBC use remained stable, whereas FFP and hemostatic agents increased, when compared with Group 1 (n=82). Increased FFP:RBC ratio (p = 0.053) and earlier administration of FFP (p = 0.001) were also observed, especially with proactive MBP triggering. Group 2 patients presented lower rates of 24-h (0.5% vs. 7.3%; p = 0.002) and 30-day mortality (15.9% vs. 30.2%; p = 0.018) - the greatest reduction corresponding to non-surgical patients. Logistic regression showed an independent protective effect of MBP implementation upon 30-day mortality (OR = 0.3; 95% CI 0.15-0.61). Conclusions: These data suggest that the implementation of a goal-directed MBP for prompt and aggressive management of non-trauma, massive bleeding patients is associated to reduced 24-h and 30-day mortality rates. (C) 2016 Elsevier Espana, S.L.U. y SEMICYUC. All rights reserved.