Discrepancy between clinical and autopsy diagnosis in children supported on extracorporeal membrane oxygenation (ECMO) has not been previously described. To assess the utility of autopsy examination in children supported on ECMO and assess discrepancies between premortem and postmortem diagnosis in these patients. Retrospective chart review. General pediatric and cardiac intensive care units (ICUs) in a tertiary children’s hospital. The hospital’s ECMO database was queried for patients supported on ECMO from 2000 through 2010 who died and underwent autopsy examination. Fifty-four autopsies were performed in 139 nonsurvivors (28%) who required ECMO support in the pediatric and cardiac ICU. Major discrepancies between premortem and postmortem diagnoses were found in 29 patients (53.7%). The commonest missed diagnosis was myocardial infarction that occurred in 16 patients, followed by adrenal hemorrhage in three patients. Five patients with a cardiac diagnosis had both major (type 1 discrepancy) and minor (type 2 discrepancy) discrepancies. Surgical complications were noted in four postmortem study with three of them being class 1 discrepancy. We report significant discrepancy between autopsy and clinical findings among ECMO-supported pediatric patients. Our findings underscore the need for enhanced premorbid surveillance in patients supported on ECMO.