OBJECTIVES: The purpose of this multicentre cohort study was to examine the relationship between antiplatelet therapy (APT) at the time of coronary artery bypass grafting (CABG) and postoperative bleeding complications, transfusion requirements and adverse cardiovascular events. METHODS: A matched-pair analysis was carried out on 6350 consecutive patients undergoing CABG at the three university hospitals in Western Denmark. Patients exposed to aspirin or clopidogrel within 5 days before surgery were compared with those not exposed to these drugs. The data used in the study were retrieved from the Western Denmark Heart Registry. RESULTS: Of the 6350 patients enrolled, 1846 (29%) had been exposed to aspirin or clopidogrel within 5 days prior to CABG (the APT group). Matching with the remaining 4504 (71%) patients of the control group resulted in 1132 pairs of patients. Patients in the APT group had greater mean chest tube drainage volumes (946 vs 775 ml; P<0001) and greater transfusion requirements (ranging from 37.4-57.5 vs 29.8%; P <0.0001) than control group patients. Preoperative aspirin therapy was not associated with greater reoperation rates (4.0 vs 3.9%; P= 0.005); nor was it an independent risk factor for severe postoperative bleeding >1000 ml (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.55-1.34). Preoperative clopidogrel use, on the other hand, was associated with greater reoperation rates (10.2 vs 3.9% in the control group; P= 0.005) and was an independent predictor of severe postoperative bleeding (OR: 2.08, 95% CI: 1.55-2.80). Overall, preoperative APT had no significant effect on postoperative 30-day mortality, incidence of myocardial infarction, stroke or need for dialysis. CONCLUSIONS: Preoperative APT is associated with increased bleeding and greater transfusion requirements after CABG. Clopidogrel exposure is associated with greater reoperation rates and is an independent risk factor for severe postoperative bleeding.