Aspirin administration before cardiac surgery represents a balance between preventing perioperative thrombotic events and promoting surgical bleeding. Clear evidence to guide the preoperative use of aspirin in patients undergoing cardiac surgery is lacking. This systematic review and meta-analysis was performed to evaluate the efficacy and safety of preoperative aspirin, in patients undergoing coronary artery surgery. Methods We conducted a systematic review and meta-analysis of randomized trials involving patients undergoing coronary artery surgery assigned to preoperative aspirin therapy or no aspirin/placebo. The MEDLINE and EMBASE databases and Cochrane Central Register of Controlled Trials were searched up to March 2014 without language restrictions. Two reviewers performed independent quality review and data extraction. Efficacy outcomes of myocardial infarction (MI) and mortality, and safety outcomes of blood loss, red cell transfusion, and surgical re-exploration were compared. Results In 13 trials (n=2399), preoperative aspirin therapy reduced the risk of MI (OR, 0.56; 95 CI, 0.33-0.96; P=0.03), without a reduction in mortality (OR, 1.16; 95 CI, 0.42-3.22; P=0.77). Preoperative aspirin increased postoperative chest tube drainage (mean difference 168 ml; 95 CI, 39-297 ml; P=0.01), red cell transfusion (mean difference 141 ml; 95 CI, 55-226; P=0.001) and need for surgical re-exploration (OR, 1.85, 95 CI, 1.15-2.96; P=0.01). Studies were of low methodological quality, with significant heterogeneity identified. Conclusions In patients undergoing coronary artery surgery, preoperative aspirin reduces perioperative MI, but at a cost of increased bleeding, blood transfusion, and surgical re-exploration.