Initial reports described a hypercoagulable state and an increased risk of thrombosis in patients who tested positive for SARS-CoV-2. Infected patients with severe acute respiratory distress syndrome in the setting of coronavirus disease 2019 (COVID-19) may require extracorporeal membrane oxygenation (ECMO), leading to coagulopathies and further increasing the risk for bleeding and thrombosis. We conducted a single-center retrospective cohort study to compare the incidence of major bleeding and thrombosis in COVID-19 versus influenza-positive patients requiring ECMO. There was no difference in the incidence of major bleeding (67.7% vs. 85.7%, p = 0.287) or major thrombosis (9.7% vs. 21.4%, p = 0.356) between COVID-19 and influenza patients, respectively. COVID-19 patients experienced significantly fewer major bleeding events per ECMO days compared with influenza (0.1 [interquartile range 0–0.2] vs. 0.2 [interquartile range 0.1–0.5], p = 0.026). Influenza patients may be at higher risk for developing coagulopathies that contribute to bleeding. Larger evaluations are needed to confirm these results and further assess bleeding and thrombosis risk in these populations.