Epsilon-aminocaproic acid and tranexamic acid, two synthetic antifibrinolytics, and aprotinin, an antifibrinolytic derived from bovine lung, are used to reduce excessive bleeding and transfusion of homologous blood products (HBP) after cardiac surgery. This review analyzes the studies on the utilization of antifibrinolytics in adult cardiac surgery according to the epidemiological concepts of efficacy, effectiveness and efficiency. A majority of published studies confirm the efficacy of antifibrinolytics administered prophylactically to reduce postoperative bleeding and transfusion of HBP. More studies are needed, however, to compare antifibrinolytics and determine if any one is superior to the others. Despite their demonstrated efficacy, antifibrinolytics are only one of the options available to diminish the use of HBP. Other blood-saving techniques, surgical expertise, temperature during cardiopulmonary bypass and respect of established transfusion guidelines may modify the effectiveness of antifibrinolytics to the point where antifibrinolytics may not be necessary. At this time, insufficient data have been published to perform a cost vs benefit analysis of the use of antifibrinolytics. This complex analysis takes into account not only direct costs (cost of the drug and of blood products), but also the ensuing effects of treatments such as: length of stay in the operating room, in the intensive care unit and in the hospital; need for surgical re-exploration; treatment of transfusion or drug-related complications, etc. In particular, the risk of thrombotic complications associated with antifibrinolytics is the subject of an ongoing, unresolved controversy. In conclusion, it is important for each institution to determine if their patient population (or a subset of this population) is likely to benefit from prophylactic treatment with antifibrinolytics, and to confirm that treatment is not associated with an increased incidence of untoward effects, before engaging in the routine use of any of these medications.