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Extracorporeal membrane oxygenation (ECMO) use is increasing worldwide, driven by device simplification and increasing need during the coronavirus disease 2019 (COVID-19) pandemic, while bleeding and thrombotic events remain a major challenge. An analysis of 7579 veno-venous ECMO (VV-ECMO) patients from 2010 to 2017 in the Extracorporeal Life Support Organization (ELSO) database reported that 40.2% experienced one or more bleeding or thrombotic event, with circuit thrombosis the most common in 54.9% of events [1]. Comparatively, an analysis of 11,984 veno-arterial (VA-ECMO) patients from the same database reported 8,457 events, of which 62.1% were bleeding events [2]. Balancing anticoagulation to prevent thrombotic complications against bleeding in these complex critically ill patients during ECMO is an ongoing challenge for clinicians. In this pragmatic state-of-the-art summary, we review managing anticoagulation in ECMO.