Empyema resulting as a complication of penetrating diaphragmatic injuries is a subject that requires further investigation, and the aim of this study was to determine the risk factors associated with empyema in patients with penetrating trauma. Consecutive adult trauma patients from a level 1 trauma center were searched for penetrating diaphragm injuries. Data were collected on patient demographics, pre-existing conditions, injury type and severity, hospital interventions, in-hospital complications, and outcomes. Patients were stratified by empyema formation and univariant analyses were performed. 164 patients were identified, and 17 patients (10.4%) developed empyema. Empyema was associated with visible abdominal contamination (35.3% vs 15%, P = .04), thoracotomy (35.5% vs 13.6%, P = .03), pneumonia (41.2% vs 14.3%, P = .01), sepsis (35.3% vs 8.8%, P = .006), increased hospital length of stay (25.5 vs 10.1 days, p =<.001), increased intensive care unit length of stay (9.6 vs 4.3 days, P = .01), and decreased in-hospital mortality (0% vs 20.4%, P = .04).