Inferior vena cava (IVC) injuries are associated with significant morbidity and mortality. To identify clinical factors associated with mortality in patients undergoing operative intervention for penetrating IVC injuries, a retrospective review of 98 patients was performed, excluding blunt injuries (n = 20) and deaths before surgery (n = 16). The overall mortality was 58 per cent. Nonsurvivors more commonly presented with hypotension (50% vs 23%, P = 0.03) and underwent resuscitative thoracotomy more frequently (42% vs 4%, P = 0.01). Retrohepatic injuries were more common among nonsurvivors (P = 0.04). There was no difference in the use of ligation (7% vs 17%, P = 0.29) or the massive transfusion protocol (35% vs 25%, P = 0.41). On multivariate analysis, after controlling for mechanism of injury, admission hypotension, Glasgow Coma Scale score , preoperative cumulative fluids, resuscitative thoracotomy , absence of spontaneous tamponade, and location of IVC injury, the only independent predictor of mortality was the absence of spontaneous tamponade at the time of laparotomy (odds ratio = 5.4, 95% confidence interval: 1.11-25.95; P = 0.04). Penetrating IVC injuries continue to be associated with a high mortality, particularly among patients with free intraabdominal hemorrhage at laparotomy. Large multicenter studies are required to define the optimal resuscitative and operative management techniques in these severely injured patients.