Introduction End tidal CO2 (ETCO2) has been established as a standard for confirmation of an airway, but its role is expanding. In certain settings ETCO2 closely approximates the partial pressure of arterial CO2 (PaCO2) and has been described as a tool to optimize a patient's ventilatory status. ETCO2 monitors are increasingly being used by EMS personnel to guide ventilation in the prehospital setting. Severely traumatized and burn patients represent a unique population to which this practice has not been validated. Hypothesis The sole use of ETCO2 to monitor ventilation may lead to avoidable respiratory acidosis. Methods A consecutive series of patients with burns or trauma intubated in the prehospital setting over a 24-month period were evaluated. Prehospital arrests were excluded. Absence of ETCO2 transport data and patients without an arterial blood gas (ABG) within 15 minutes of arrival were also excluded. Data collected included demographics, place and time of intubation, service performing intubation, ETCO2 maintained en-route to hospital, and ABG upon arrival. Further data included length of stay, mortality, and injury severity scores. Results One hundred sixty patients met the inclusion criteria. Prehospital ETCO2 did not correlate with measured PaCO2 (R2 = 0.08). Mean ETCO2 was significantly lower than mean PaCO2 (34 mmHg vs 44 mmHg, P <.005). Patients arriving acidotic were more likely to die. Mean pH on arrival for survivors and decedents was 7.32 and 7.19 respectively (P <.001). Mortality, acidosis, higher base deficits, and more severe injury patterns were all predictors for a worse correlation between ETCO2 and PaCO2 and increased mean difference between the two values. Decedents and patients presenting with a pH <7.2 demonstrated the greatest discrepancy between ETCO2 and PaCO2. The data suggest that patients may be hypoventilated by prehospital providers in order to obtain a prescribed ETCO2. Conclusion ETCO2 is an inadequate tool for predicting PaCO2 or optimizing ventilation in severely injured patients. Adherence to current ETCO2 guidelines in the prehospital setting may contribute to acidosis and increased mortality. Consideration should be given to developing alternate protocols to guide ventilation of the severely injured in the prehospital setting. Copyright © World Association for Disaster and Emergency Medicine 2013.