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Background Recent studies have presented contradictory findings on the relationship between blood type and mortality in trauma patients. Using the largest population in a study of this type to date, we hypothesized that ABO genotype and Rhesus status would influence trauma-related mortality and morbidity given the relationship between blood type and hemostasis.Methods Data from all trauma patients admitted to level I and level II trauma centers in one city over a five-year period was retrospectively analyzed. Patients were stratified by ABO type. Patient demographics and outcomes were then assessed. Chi-squared and Fisher’s exact tests were used to analyze categorical variables. Continuous variables were analyzed using ANOVA or Kruskal-Wallis tests as appropriate. Logistic regression was used to determine independent associations for 28-day mortality and complications.Results Of 5249 patients, severe injury (ISS >15) was present in 1469. Approximately one-quarter of patients with severe injury received blood products within the first 24 hours. There were no significant variations in demographics or complications between patients of different blood types. Univariate and multivariable regression analysis showed no association between blood type and mortality. However, penetrating injury, lower GCS, higher ISS, blood transfusion within 24 hours, and Asian descent were associated with higher overall mortality.Conclusions In contrast to previous studies, we found no evidence of an association between blood type and mortality. However, our findings suggest that patients of Asian descent may be at higher risk for mortality following trauma. Further research is warranted to explore this observation.