Redo-sternotomy and aortic valve replacement in patients with advanced liver disease is rare and associated with a prohibitive morbidity and mortality. Refractory coagulopathy is common and a consequence of intense activation of the coagulation system that can be triggered by contact of blood with the cardiopulmonary bypass circuitry, bypass-induced fibrinolysis, platelet activation and dysfunction, haemodilution, surgical trauma, hepatic decompensation and hypothermia. Management can be further complicated by right heart dysfunction, porto-pulmonary hypertension, poor myocardial protection, and hepato-renal syndrome. Complex interactions between coagulation/fibrinolysis and systemic inflammatory response syndrome reactions like “post-perfusion-syndrome” also compound haemostatic failure. Given the limited information available for the specific management and prevention of cardiopulmonary bypass-induced haemostatic failure, this report serves to guide the anaesthesia and medical management of future cases of a similar kind. We discuss our multimodal management of haemostatic failure using pharmacological strategies, thromboelastography, continuous cerebral and liver oximetry, and continuous cardiac output monitoring.