BACKGROUND: This systematic review examines the occurrence and implications of resistance to primary antiplatelet agents, aspirin and clopidogrel, often utilised in patients undergoing coronary artery bypass grafting (CABG), alongside the methodologies for assessment of such resistance. METHODS: An extensive literature search across various databases such as PubMed, MEDLINE via Ovid, Embase, and Cochrane CENTRAL until May 2024 was conducted to identify studies evaluating antiplatelet resistance in on-pump and off-pump CABG patients. Following quality assessment, only high-quality studies were incorporated into this review. RESULTS: This review included 19 studies with 3,915 patients, four of which were randomised controlled trials and 15 were observational studies. Aspirin resistance incidence ranged from 11.0% to 51.5%, while clopidogrel resistance was 22%. Antiplatelet resistance, assessed through a wide variety of methods, was associated with a 13 times increase in the risk of vein graft occlusion and increased rates of mortality, myocardial infarction, and target vessel revascularisation in the case of clopidogrel resistance. The effect of cardiopulmonary bypass on antiplatelet resistance remains ambiguous. CONCLUSION: The academic literature lacks a standardised definition for antiplatelet resistance. Assessment methodologies greatly vary, leading to noninterchangeable outcomes. While aspirin resistance has a conflicting overall significant impact on adverse outcomes, clopidogrel resistance correlates with poorer clinical outcomes.