Clopidogrel is recommended with aspirin for patients who undergo coronary artery bypass grafting (CABG) after non-ST elevation myocardial infarctions. Cardiothoracic surgeons widely use clopidogrel in addition to aspirin for post-CABG patients, including those with stable coronary artery disease. The aim of this study was to systematically review the published research to determine whether clopidogrel use after CABG is based on good trial data. Studies reporting safety and/or efficacy data for clopidogrel use with or without aspirin after on- or off-pump CABG were included. Fourteen studies met the inclusion criteria, of which 11 were reported trials and 3 are ongoing trials. Subgroup retrospective analyses of previously reported large trials of patients presenting with acute coronary syndromes (n = 1) or patients with stable coronary artery disease (n = 3) did not show a clear clinical benefit of clopidogrel when given in addition to aspirin after CABG. In contrast, there was a trend toward increased major and minor bleeding after the use of clopidogrel plus aspirin. Two small prospective trials providing data on surrogate end points and 5 small trials involving off-pump CABG patients were not of good quality to draw meaningful conclusions. In conclusion, summarized data based on subgroup analyses, surrogate end points, and observational cohort studies fail to demonstrate a clear beneficial effect of clopidogrel alone or in combination with aspirin on clinical outcomes after CABG.