Emergency department thoracotomy (EDT) is done to control life threatening hemorrhage and injuries. Literature examining this topic is limited to relatively small studies from single trauma centers. This study identifies factors associated with survival to hospital discharge of patients undergoing EDT using the largest U.S. national trauma database. This retrospective cohort study used the U.S. National Trauma Data Bank 2015. We conducted univariate and bivariate analyses followed by a multivariate analysis that adjusted for confounders to identify factors associated with survival. Two thousand four hundred eighty-six patients who underwent EDT were included. Most patients were 16 to 64 years of age (92.3%) with a male predominance (84.9%) and without any previous comorbidities (62.8%). Penetrating injury was most common (60.2%), mainly as a result of assault (51.0%) by firearm (45.1%). Overall survival to hospital discharge was 38.2%. After adjusting for confounders, factors associated with increased survival were cut/piece injuries, presenting with signs of life, Glasgow Coma Scale score ≥8, systolic blood pressure >90 mm Hg, and transportation to the ED through helicopter/fixed-wing ambulance or public/private vehicle (reference, ground ambulance). Factors associated with survival in patients undergoing EDT were identified. The clinical indication of presence of appropriate resources to continue and repair EDT was validated, along with the contraindications of lack of signs of life and presence of major nonsurvivable injuries. Future studies should focus on validation of all criteria of EDT, namely hemodynamic instability despite appropriate fluid resuscitation, duration of time of cardiopulmonary resuscitation and pulselessness, cardiac rhythm on arrival, and the presence of pericardial tamponade.