Background: The incidence rate of extracorporeal membrane oxygenation (ECMO) use in Taiwan has increased significantly and is now higher than the worldwide incidence since 2000. Several studies have investigated hospital mortality and the risk factors of patients receiving ECMO. Comorbidities and age were not evaluated in these studies. Aim: To investigate the impact of age and comorbidities on hospital mortality of ECMO patients. Methods: A retrospective study of ECMO patients was performed using the claims data from the Taiwan National Health Insurance Research Database. Results: A total of 5834 adult patients were included in the study, and 2270 patients (38.9%) were discharged from the hospital between 2004 and 2012. The most common comorbidities were coronary artery disease (35.7%), hypertension (32.0%), and acute myocardial infarction (28.4%). Age, interstitial lung disease, rheumatologic disease, and lymphoma were the major predictors for hospital mortality in ECMO patients. On the contrary, acute myocarditis was found to be a favorable factor. Conclusion: Our results indicated that age and comorbidities were strongly associated with hospital mortality among ECMO patients. These findings can assist ECMO specialists to improve evaluations of mortality risk, especially among elderly patients with specific comorbidities.