Definitive laparotomy (DL) for penetrating abdominal wounding with combined vascular and visceral injury is a difficult surgical challenge. Physiologic derangements such as dilutional coagulopathy, hypothermia, and acidosis often preclude completion of the procedure. “Damage control” (DC), defined as initial control of hemorrhage and contamination followed by intraperitoneal packing and rapid closure, allows for resuscitation to normal physiology in the intensive care unit and subsequent definitive re-exploration. The purpose of the study was to compare the damage control technique with definitive laparotomy. Over a 3 1/2-year period, 46 patients with penetrating abdominal injuries required laparotomy and urgent transfusion of greater than 10 units packed red blood cells for exsanguination. Medical records were retrospectively reviewed for degree and pattern of injury, probability of survival, actual survival, transfusion requirements for the preoperative and postoperative phases, resuscitation and operative times, lowest perioperative temperature, pH, and HCO3. No significant differences were identified between 22 DL and 24 DC patients and actual survival rates were similar (55% DC vs. 58% DL). However, in a subset of 22 patients with major vascular injury and two or more visceral injuries (maximum injury subset), otherwise similar to the overall group, survival was markedly improved in patients treated with damage control (10 of 13, 77%*) vs. DLM (1 of 9, 11%) (Fisher's exact test*p < 0.02). In preparation for return to the operating room, DC survivors averaged 8.4 units of packed red blood cells transfused and 10.3 units fresh frozen plasma over a mean ICU stay of 31.7 hours. Resolution of coagulopathy (mean prothrombin time/partial thromboplastin time 19.5/70.4 to 13.3/34.9), normalization of acid-base balance (mean pH/HCO3 7.37/20.6 to 7.42/24.2), and core rewarming (mean 33.2°C to 37.7°C) were achieved. All patients had gastrointestinal procedures at reoperation (mean operative time, 4.3 hours). We conclude that damage control is a promising approach for increased survival in exsanguinating patients with major vascular and multiple visceral penetrating abdominal injuries.