OBJECTIVES: To characterize epidemiological risk factors, review clinical outcomes, and overall costs associated with treating bleeding related to cardiac surgery, and identify areas for further research. METHODS: A systematic literature search was performed (1996-March 2007) using terms designed to identify publications describing epidemiology and associated risk factors, clinical outcomes, and economic impact of bleeding in cardiac surgery patients. Studies were identified through electronic Medline® and PubMed® searches. Manual review of bibliographies within these papers allowed identification of additional articles. RESULTS: A total of 36 (epidemiology: n=13, clinical outcomes: n=14, and economic burden: n=9) papers [manual search: n=12] were included for review. Incidence of bleeding associated with major cardiac surgical procedures varied widely, ranging from 0.4%-19.0%, partly attributable to the types of cardiac operations as well as to differences in the definition of bleeding. Pre-operative smaller body mass index, use of antithrombotic drugs, nonelective surgery, increased age, and redo procedures were associated with bleeding, while embolic events were found to be major complications. Costs associated with bleeding requiring transfusion ranged from $397 (blood products only) to $10,225 per patient (all treatment costs), with hospital LOS as the major cost contributor. Mean cost of open-heart surgeries [including coronary artery bypass graft (CABG) and valve replacements] range from $25,057 to $79,795, with patients undergoing CABG found to have an incremental cost of $3,866 associated with bleeding. Primary pharmacological treatments for bleeding among cardiac surgery patients included antifibrinolytics and procoagulants. CONCLUSION: Post-operative bleeding remains a central clinical outcome in cardiac surgery with significant economic impact despite improvements in peri-operative bleeding management. Sufficient information on recent cost estimates as well as differences in bleeding costs associated with various cardiac procedures is lacking. Further research investigating the economic consequences of bleeding associated with cardiac surgery is warranted.