Despite advanced techniques and improved clinical outcomes, patient survival following coronary artery bypass grafting (CABG) is still a major concern. Therefore, predicting future CABG mortality represents an unmet medical need and should be carefully explored. The objective of this study is to assess whether pre-CABG platelet activity corresponds with 30 days mortality post-CABG. Retrospective analyses of platelet biomarkers and death at 30 days in 478 heart surgery patients withdrawn from aspirin or/and clopidogrel. Platelet activity was assessed prior to CABG for aspirin (ASPI-test) with arachidonic acid and clopidogrel (ADP-test) utilizing Multiplate impedance aggregometer. Most patients (n = 198) underwent conventional CABG, off-pump (n = 162), minimally invasive (n = 30), artificial valve implantation (n = 48) or valves in combination with CABG (n = 40). There were 22 deaths at 30 days, including 10 in-hospital fatalities. With the cut-off value set below 407 area under curve (AUC) for the ASPI-test, the 30-day mortality was 5.90% for the lower cohort and 2.66% for patients with significantly higher platelet reactivity (P = 0.038). For the ADP-test with a cut-off at 400AUC, the 30-day mortality was 9.68% for the lower cohort and 3.66% for patients with higher platelet reactivity, representing a borderline significant difference (P = 0.046). Aside from the platelet indices, patients who received red blood cell (RBC) concentrate had a highly significant (P < 0.0001) risk of death at 30 days. Both aspirin and clopidogrel tests were useful in predicting 30 days mortality following heart surgery, suggesting the danger of diminished platelet activity prior to CABG in such high-risk patients. These preliminary evidence supports early discontinuation of antiplatelet therapy for elective CABG and requires adequately powered randomized trials to test the hypothesis and potentially improve survival.