This study characterizes the burden and outcomes of ECMO use in U.S. hospitalizations during the pandemic, analyzing 17,520 cases from the National Inpatient Sample between 2019 and 2020. It highlights a significant increase in ECMO utilization, with a marked impact on inpatient mortality, length of hospital stay, and healthcare costs. Predominantly affecting patients with circulatory and respiratory diseases, ECMO hospitalizations showed a higher mortality rate (43.1%) compared to non-ECMO cases (2.1%), with an average hospital stay of 26 days and an average cost of US$967,647 per case. Factors like Hispanic descent, higher CCI score, age over 60, and a higher APRDRG risk were associated with increased mortality.