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Venoarterial extracorporeal membrane oxygenation (VA ECMO) has been increasingly applied in patients with cardiogenic shock in recent years. Nevertheless, many patients cannot be successfully weaned from VA ECMO support and 1-year mortality remains high. A systematic approach could help to optimize clinical management in favor of weaning by identifying important factors in individual patients. Here, we provide an overview of pivotal factors that potentially prevent successful weaning of VA ECMO. We present this through a rigorous approach following the relatable acronym ABCDE, in order to facilitate widespread use in daily practice.