Background: Prehospital emergency medical services (EMS) are the main gateway for trauma patients. Recent advances in point-of-care testing and the development of early warning scores have allowed EMS to improve patient classification. We aimed to identify patients presenting with major trauma involving life-saving interventions (LSI) using the modified Sequential Organ Failure Assessment (mSOFA) score in the prehospital scenario, and to compare these results with those of other trauma scores. Methods: This was a prospective, ambulance-based, multicenter, training-validation study in trauma patients who were treated in a prehospital setting and subsequently transported to a hospital. The study involved six Advanced Life Support units, 38 Basic Life Support units, and four hospitals. The primary outcome was LSI performed at the scene or en route and intensive care unit (ICU) admission and all-cause two-day in-hospital mortality. We collected epidemiological variables, creatinine, lactate, base excess, international normalized ratio, and vital signs. Discriminative power (area under the receiver operating characteristic curve [AUC]), calibration (observed vs predicted outcome agreement), and decision-curve analysis (DCA, clinical utility) were used to assess the reliability of the mSOFA in comparison to other scores. Results: Between January 1, 2020-April 30, 2022, a total of 763 patients were selected. The mSOFA score's AUC was 0.927 (95% confidence interval [CI] 0.898-0.957) for LSI, 0.845 (95% CI 0.808-0.882) for ICU admission, and 0.979 (95% CI 0.966-0.991) for two-day mortality. Conclusion: The mSOFA score outperformed the other scores, allowing a quick identification of high-risk patients. The routine implementation in EMS of mSOFA could provide critical support in the decision-making process in time-dependent trauma injuries.