BACKGROUND: Hemorrhage is a leading cause of death after trauma and childbirth. In response to severe hemorrhage, bleeding patients often receive transfusions of red blood cells, plasma, platelets, or other blood components. We examined risk factors for transfusion in acute severe bleeding in two trials of over 20,000 patients to better understand factors associated with transfusion likelihood. STUDY DESIGN AND METHODS: We conducted a cohort analysis of data from the CRASH-2 and WOMAN trials, two multinational trials that recruited patients with traumatic and postpartum hemorrhage, respectively. For each trial, we examined the effect of 10 factors on blood transfusion likelihood. Univariate and multivariate Poisson regressions were used to analyze the relationship between risk factors and blood transfusion. RESULTS: Of the 20,207 traumatic hemorrhage patients, 10,232 (51%) received blood components. Of the 20,060 women with postpartum hemorrhage, 10,958 (55%) received blood components. For patients who suffered from traumatic hemorrhage, those greater than three hours from injury to hospitalization were more likely to be transfused (ARR 1.37; 95% CI, 1.20-1.56). Postpartum hemorrhage patients had an increased likelihood of transfusion if they gave birth outside the hospital (ARR 1.30; 95% CI 1.22-1.39), gave birth more than three hours before hospitalization (ARR 1.09; 95% CI 1.01-1.17), had a Caesarean section (ARR 1.16; 95% CI 1.08-1.25), and if they had any identifiable causes of hemorrhage other than uterine atony. CONCLUSION: Several risk factors are associated with an increased likelihood of transfusion in traumatic and postpartum hemorrhage patients. Altering modifiable factors, by reducing time from injury or childbirth to hospitalization, for example, might be able to reduce transfusions and their complications. TRIAL REGISTRATION: CRASH-2 is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919. WOMAN is registered as ISRCTN76912190, ClinicalTrials.gov NCT00872469, PACTR201007000192283, and EudraCT number 2008-008441-38.