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The outcome of extracorporeal membrane oxygenation (ECMO) might be influenced by its complications. Only limited information is available regarding the pathologic consequences of ECMO, especially in the era of modern ECMO technology.We studied the histopathologic findings in autopsy lungs of patients treated with ECMO compared with those without ECMO. Autopsy files were queried for cases with ECMO. An age- and sex-matched control group comprised of patients who died in the ICU without acute respiratory distress syndrome, pneumonia, or ECMO was compared with patients with ECMO for cardiac reason. Histopathology and medical records were reviewed.Seventy-six patients treated with ECMO (38 men; median age, 40 years) and 47 control patients (23 men; median age, 45 years) were included. Common histologic pulmonary findings in the ECMO group were pulmonary hemorrhage (63.2%), acute lung injury (60.5%), thromboembolic disease (47.4%), calcifications (28.9%), vascular changes (21.1%), and hemorrhagic infarct (21.1%). Pulmonary hemorrhage was associated with longer ECMO duration (median, 7.0 vs 3.5 months; P = .014), acute lung injury with venovenous ECMO (91.7% vs 54.7%; P = .039) and longer ECMO (6.0 vs 4.0 months; P = .044), and pulmonary calcifications with infants (50.0% vs 22.4%; P = .024). Patients with ECMO for cardiac reasons (n = 60) more frequently showed pulmonary hemorrhage (P < .001), diffuse alveolar damage (P = .044), thromboembolic disease (P = .004), hemorrhagic infarct (P = .002), pulmonary calcifications (P = .002), and vascular changes (P = .001) than patients in the non-ECMO group.Some findings are suspected to be associated with the patient's underlying disease, whereas others might be related to ECMO. Our results provide a better understanding of ECMO-related lung disease and might help to prevent it.