Congenital diaphragmatic hernia (CDH) and its attendant lack of abdominal domain can create major technical challenges with respect to diaphragmatic and abdominal wall reconstruction, especially in seriously ill infants who require extracorporeal membrane oxygenation (ECMO). The authors reviewed the medical records of all infants with CDH repaired on ECMO at their institution (group 1, 15 patients), and compared them with infants having CDH repair before ECMO (group 2, 20 patients) and with those who had CDH repair but did not require ECMO (group 3, 15 patients). Thirty-seven of 50 patients survived (74%): 10 in group 1, 12 in group 2, and all 15 in group 3. There was a statistically significant difference (P < .001) with respect to the requirement of a polytetrafluoroethylene (PTFE) diaphragmatic patch for patients in group 1 versus those in both groups 2 and 3. There was also a significant difference in the number of patients in whom the abdomen could not be closed (P < .001 for group 1 v groups 2 and 3). Infants who require ECMO before CDH repair are more likely to have large diaphragmatic defects that require prosthetic reconstruction, and abdominal wall closure problems resulting from loss of abdominal domain, which further complicate the management of the physiological derangements from pulmonary hypoplasia and persistent pulmonary hypertension.