OBJECTIVES: Recent guidelines suggest that patients undergoing coronary artery bypass grafting (CABG) should discontinue clopidogrel and aspirin (ASA) 5 and 2-10 days, respectively, before surgery to reduce postoperative bleeding and its complications. The aim of our study was to evaluate the relationship between the timing of discontinuing clopidogrel + ASA and early clinical outcomes in patients undergoing CABG. METHODS: Four thousand three hundred and thirty consecutive patients underwent isolated CABG from April 2004 to February 2009. Of these, 926 patients received double antiplatelet therapy in the 14 days prior to surgery. Patients were stratified into three groups: clopidogrel + ASA within 5 and 2 days, respectively, before surgery (Group A, n = 287); clopidogrel within 5 days + ASA stopped 2-10 days before surgery or clopidogrel stopped 5 days + ASA within 2 days of surgery (Group B, n = 308) and clopidogrel + ASA discontinued >5 and 10 days, respectively, before surgery (control group, n = 331). RESULTS: Overall mortality was 0.8%. The incidence of postoperative myocardial infarction (MI) was 5.2, 1 and 1.8% in Groups A, B and control, respectively (P = 0.004). Reoperation for bleeding occurred in 4.5, 2.9 and 1.2% (P = 0.04) and total chest drainage was 761 ± 473, 720 ± 421 and 687 ± 302 ml in Groups A, B and control, respectively (P = 0.06). Multivariable analysis revealed that Group A was an independent predictor of postoperative MI (P = 0.02), reoperation for bleeding (P = 0.02), blood transfusions (P = 0.003) and blood losses (P = 0.015). CONCLUSIONS: Clopidogrel in combination with ASA up to the time of surgery is associated with an increased risk of postoperative MI, blood loss and reoperation for bleeding in patients undergoing CABG.