Background Barriers to trauma care for rural populations are well documented, but little is known about the magnitude of urban-rural disparities in injury mortality. This study sought to quantify differences in injury mortality comparing rural and nonrural residents with traumatic injuries. Methods Using data from the 2009–2010 Nationwide Emergency Department Sample, multiple logistic regression analyses were conducted to estimate odds of death after traumatic injury for rural residents compared with nonrural residents, while controlling for age, sex, injury type and severity, comorbidities, trauma designation, and Census region. Results Rural residents were 14% more likely to die after traumatic injury compared with nonrural residents (P < .001). Increased odds of death for rural residents were observed at level I (odds ratio = 1.20, P < .001), level II (odds ratio = 1.34, P < .001), and level IV/nontrauma centers (odds ratio = 1.23, P < .001). The disparity was greatest for injuries occurring in the South and Midwest (odds ratio = 1.54, P < .001 and odds ratio = 2.06, P < .001, respectively) and for cases with an injury severity score <9 or unknown severity (odds ratio = 2.09, P < .001 and odds ratio = 1.31, P < .001, respectively). Conclusion Rural residents are significantly more likely than nonrural residents to die after traumatic injury. This disparity varies by trauma center designation, injury severity, and US Census region. Distance and time to treatment likely play a role in rural injury outcomes, along with regional differences in prehospital care and trauma system organization.