BACKGROUND 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. 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 scores for the thorax (P < 0.001), lower lowest systolic blood pressure before intensive care unit 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 Abbreviated Injury Scale score for the thorax (P = 0.001) and a lower lowest systolic blood pressure before intensive care unit 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.