Improvements in trauma care require a better understanding of pre-existing medical conditions (PEMC). The presence, type and effect of PEMC in trauma victims were assessed using data from the United Kingdom Major Trauma Outcome Study (UK MTOS). Complete records were available in 13,198 (39%) patients and 5129 (38.8%) of these had at least one PEMC. The analysis of comprehensive records from 1471 injured patients treated at one participating hospital showed that the incidence of PEMC increased with age. PEMC were found to be an independent risk factor influencing mortality after controlling for age, Injury Severity Score (ISS) and Revised Trauma Score (RTS). Odds of death were approximately doubled in the presence of PEMC and increased up to seven fold if four or more PEMC were present. Pre-existing cardiovascular and metabolic disease significantly increased mortality. As these conditions influence initial assessment and treatment response, an accurate medical history is essential to facilitate identification and treatment.