Cardiac surgery is associated with a systemic inflammatory response and systemic coagulopathy, which can result in significant organ dysfunction and bleeding. Aprotinin, a serine protease inhibitor, can limit systemic inflammation, and has been associated with myocardial, pulmonary and cerebral protection in addition to its proven haemostatic efficacy. Data are currently conflicting regarding the haemostatic efficacy of aprotinin relative to alternative agents including tranexamic acid. Recent studies have demonstrated aprotinin usage is associated with increased rates of thrombotic and renal complications, but these findings are at odds with the majority of studies relating to aprotinin safety to date. The lack of adequately powered, randomised studies evaluating aprotinin and alternative agents limits drawing conclusions about the complete use or disuse of aprotinin presently and requires individualised patient selection based on bleeding risk and co-morbidities for its usage.