Rationale: The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that can develop at various times after major trauma. Objective: To identify and characterize distinct phenotypes of ARDS after trauma based on timing of syndrome onset. Methods: Latent class analyses were used to identify patterns of ARDS onset in a cohort of critically ill trauma patients. Identified patterns were tested for associations with known ARDS risk factors and associations were externally validated at a separate institution. Eleven plasma biomarkers representing pathophysiologic domains were compared between identified patterns in the validation cohort. Main Results: Three patterns of ARDS were identified; class I (52%) early onset on day 1 or 2, class II (40%) onset on days 3 and 4, and class III (8%) later onset on days 4 and 5. Early onset ARDS was associated with higher Abbreviated Injury Scale (AIS) scores for the thorax (p<0.001), lower lowest systolic blood pressure (SBP) prior to ICU admission (p=0.003), and a greater red blood cell transfusion requirement during resuscitation (p=0.030). In the external validation cohort, early onset ARDS was also associated with a higher AIS thorax (p=0.001) and a lower lowest SBP prior to ICU enrollment (p=0.006). In addition, the early onset phenotype demonstrated higher plasma levels of soluble receptor for advanced glycation end-products and angiopoietin-2. Conclusions: Degree of hemorrhagic shock and severity of thoracic trauma are associated with an early onset phenotype of ARDS after major trauma. Lung injury biomarkers suggest a dominant alveolar-capillary barrier injury pattern in this phenotype.