STUDY DESIGN.: Retrospective cohort study. OBJECTIVE.: To identify predictors of early mortality following traumatic spinal cord injury (TSCI). SUMMARY OF BACKGROUND DATA.: Limited information is available on factors associated with early mortality following TSCI. Ability to identify high risk individuals can help to appropriately treat them, and reduce mortality. METHODS.: Early mortality was defined as death occurring during the initial hospital admission. Retrospective analysis of 1995 patients with TSCI, admitted to various hospitals of South Carolina from 1993 to 2003, was performed. There were 251 patients with early mortality. Multivariable logistic regression was used in modeling of early death following TSCI with gender, race, age, Frankel grade, trauma center, level of injury, injury severity score (ISS), traumatic brain injury (TBI), and medical comorbidities as covariates. RESULTS.: Increasing age after 20 years (OR: 1.2, P = <0.0001), male gender (OR: 1.6, P = 0.016), severe (ISS > or =15) systemic injuries (OR: 1.9, P = 0.012), TBI (OR: 3.7, P < 0.0001), 1 or more comorbidities (P < 0.0001), poor neurologic status (P = 0.015), and level 1 trauma center (OR: 1.4, P = 0.026) were significantly associated with early mortality, after adjusting for other covariates. CONCLUSION.: Early mortality following TSCI is influenced by multiple factors. Timely recognition of these factors is crucial for improving survival in the acute care setting. Severe systemic injuries, medical comorbidities, and TBI continue to be the main limiting factors affecting the outcome. These findings also suggest the need to allocate resources for trauma prevention, and promote research towards improving the care of acutely injured patients.