Background: Among older trauma patients, those with preexisting chronic medical conditions (CMCs) appear to have an elevated risk of death. Whether this association is dependent on the severity of injury or other occult factors remains unanswered. This study evaluated the association between preexisting CMCs and risk of death among older trauma patients according to injury severity. Methods: This was a retrospective cohort study using data from the National Trauma Data Bank, a registry of trauma patients admitted to 131 trauma centers across the United States. The main outcome measure was in-hospital mortality. Results: In patients 50 to 64 years of age who sustain severe (Injury Severity Score [ISS] of 26+) and moderate injuries (ISS of 16-25), the presence of one or more CMCs is not associated with an increased relative risk (RR) of death (RR, 0.80 and 95% confidence interval [CI], 0.71-0.90; RR, 1.09 and 95% CI, 0.95-1.24, respectively). Those with minor injuries (ISS < 16) have increased risk of death (RR, 2.80; 95% CI, 2.33-3.36). For those patients 65 years of age and older who sustain severe, moderate, and minor injuries, the pattern of results is similar (RR, 0.91 and 95% CI, 0.83-1.00; RR, 1.13 and 95% CI, 1.04-1.23; and RR, 1.88 and 95% CI, 1.73-2.05, respectively). Conclusions: Older trauma patients with CMCs who present with minor injuries should be considered to have an increased risk of death when compared with their nonchronically ill counterparts.