Objective:To test the hypothesis that brain injury is more common and varied in ECMO patients than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from three institutions.Methods:We conducted a retrospective multi-center observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes.Results:Forty-three subjects (n=13 female; median age=47 years) received autopsies after undergoing ECMO for ARDS (n=14), cardiogenic shock (n=14), and cardiac arrest (n=15). Median duration of ECMO was 140 hours, most decedents (n=40) received anticoagulants, 60% (n=26) underwent VA ECMO, and 40% (n=17) underwent VV ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n=17, 40%). Most pathology occurred in frontal neocortices (n=43 occurrences), basal ganglia (n=33), and cerebellum (n=26). Decedents with hemorrhage were older (median age 57 vs. 38, p=0.01), those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs. 2.0, p=0.04), and those with infarction had lower peak PaCO2 (53 vs. 61 mmHg, p=0.04). Six of nine patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n=32, 74%), and two of eight patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury.Conclusion:Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management.