Ticagrelor reduces thrombotic events compared with clopidogrel in patients with acute coronary syndrome, but may also increase bleeding complications. Coronary artery bypass grafting (CABG)-related bleeding complications have not previously been compared in clopidogrel and ticagrelor-treated patients outside the controlled environment of clinical trials. Four hundred and five consecutive CABG patients with acute coronary syndrome were included in a prospective observational study. The patients were treated with aspirin and ticagrelor (n = 173) or aspirin and clopidogrel (n = 232). Ticagrelor/clopidogrel was discontinued 5 days before surgery whenever deemed possible. Major bleeding complications according to modified blood conservation using antifibrinolytics in a randomized trial criteria (postoperative blood loss >1500 ml/12 h, re-exploration, red blood cell transfusion >10 units or death because of bleeding) were compared in all patients and when ticagrelor/clopidogrel was discontinued ≥5 days (n = 280), 2-4 days (n = 40) or 0-1 day before surgery (n = 85). Major bleeding complications did not differ significantly between ticagrelor- and clopidogrel-treated patients when all patients were compared (14.5 vs 13.8%, P = 0.89). Likewise, there were no significant differences between ticagrelor and clopidogrel when either drug was discontinued ≥5 days before surgery (6.8 vs 9.9%, P = 0.40) or 2-4 days before surgery (6.3 vs 25.0%, P = 0.21). When ticagrelor/clopidogrel was discontinued 0-1 day before surgery, there was a strong trend towards higher incidence of major bleeding in ticagrelor-treated patients (41.0 vs 21.7%, P = 0.063). There was no difference in major bleeding complications overall or when ticagrelor or clopidogrel was used in accordance with guidelines. In patients on dual antiplatelet medication up to 1 day before surgery, there tended to be more bleeding complications in ticagrelor-treated patients.