Improvement in trauma management requires a better understanding of the effect of a patient's preinjury health status on outcome. Specific historical findings and laboratory criteria were used to define pre-existing disease (PED) states and determine if they were independent predictors of fate in trauma victims. Of 7,798 adult patients admitted to a level I trauma center from July 1986 through June 1990, 16.0% (1,246) had ≥1 PED. The PED+ and PED-patients had no significant difference in Injury Severity Scores (ISSs) (15.7 versus 15.6) and admission Glasgow Coma Scale (GCS) scores (13.9 versus 13.8). The PED+ patients were older (49.2 versus 30.6 years) (p < 0.001) and had a higher mortality rate (9.2% versus 3.2%) (p < 0.001) than PED-patients. Mortality rates were also elevated for patients with ≥2 PEDs (18%) and for those with renal disease (38%), malignancy (20%), and cardiac disease (18%) (p < 0.001) compared with PED- patients. Controlling for age and ISS, there was an association between PED and mortality (Mantel-Haenszel p < 0.03). Multivariate regression showed that PED is an independent predictor of mortality (R2 = 0.1918; p < 0.0001). The greatest increases in mortality were found among patients <55 years and with ISS <20. Changes in prehospital triage criteria and outcome scoring are needed. Improvements in the management of trauma victims with chronic disease may decrease their mortality rate.