Symmetrical peripheral gangrene (multilimb ischemia without large artery occlusion) is a rare condition usually associated with disseminated intravascular coagulation, hemodynamic compromise, and/or sepsis. However, it has not been described in patients on extracorporal membrane oxygenation (ECMO). Over a 5 year period, four pediatric patients developed symmetrical peripheral gangrene on ECMO after cardiac surgery. They subsequently died and came to autopsy. History, physical examination, and laboratory studies were examined. Gross and microscopic autopsy material was reviewed. Patients were 11 days to 13 years old. Extracorporal membrane oxygenation duration was 11-22 days, and limb ischemia began 2-4 days before death. Three patients had rapid onset, with ischemia developing in <48 hours. In the fourth, ischemic changes began as focal lesions and gradually spread. Two patients were septic. Three had evidence of other end-organ damage. Pressors were used in 3 patients before the limb ischemia. Autopsies disclosed ischemic changes involving all limbs, with confluent ecchymoses. In a detailed examination in 1 case, large arteries of the extremities were patent. Involved skin and soft tissue showed bland fibrin thrombi in the microcirculation, with tissue necrosis and hemorrhage. This report describes the first 4 cases of symmetrical peripheral gangrene complicating ECMO. The 4 pediatric patients all had recent surgery for congenital cardiac disease, and all had significant exposure to ECMO prior to developing limb ischemia. Symmetrical peripheral gangrene is an unusual complication of ECMO that may arise in the setting of disseminated intravascular coagulation, sepsis, or other hemostatic and/or hemodynamic imbalance.