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Background: Deaths due to injuries exceed 4.4 million annually, with over 90% occurring in low-and middle-income countries. A key contributor to high trauma mortality is prolonged trauma-to-treatment time. Earlier receipt of medical care following an injury is critical to better patient outcomes. Trauma epidemiological studies can identify gaps and opportunities to help strengthen emergency care systems globally, especially in lower income countries, and among military personnel wounded in combat. This paper describes the methodology of the "Epidemiology and Outcomes of Prolonged Trauma Care (EpiC)" study, which aims to investigate how the delivery of resuscitative interventions and their timeliness impacts the morbidity and mortality outcomes of patients with critical injuries in South Africa., Methods: The EpiC study is a prospective, multicenter cohort study that will be implemented over a 6-year period in the Western Cape, South Africa. Data collected will link pre- and in-hospital care with mortuary reports through standardized clinical chart abstraction and will provide longitudinal documentation of the patient's clinical course after injury. The study will enroll an anticipated sample of 14,400 injured adults. Survival and regression analysis will be used to assess the effects of critical early resuscitative interventions (airway, breathing, circulatory, and neurologic) and trauma-to-treatment time on the primary 7-day mortality outcome and secondary mortality (24-h, 30-day) and morbidity outcomes (need for operative interventions, secondary infections, and organ failure)., Discussion: This study is the first effort in the Western Cape of South Africa to build a standardized, high-quality, multicenter epidemiologic trauma dataset that links pre- and in-hospital care with mortuary data. In high-income countries and the U.S. military, the introduction of trauma databases and registries has led to interventions that significantly reduce post-injury death and disability. The EpiC study will describe epidemiology trends over time, and it will enable assessments of how trauma care and system processes directly impact trauma outcomes to ultimately improve the overall emergency care system., Trial Registration: Not applicable as this study is not a clinical trial., (© 2022. The Author(s).)