Abstract Introduction Among patients undergoing coronary artery bypass grafting (CABG), in a significant group chronic anticoagulant treatment is indicated. Current recommendations from scientific societies do not clearly indicate the optimal antithrombotic treatment strategy in this group of patients. Addition of antiplatelet therapy recommended after CABG to chronic anticoagulant therapy increases the risk of bleeding complications, however, efficacy of antithrombotic treatment strategies has not been compared in large prospective studies. Purpose The aim of the study was to compare the efficacy and safety of post-CABG antithrombotic treatment strategies in patients after CABG with coexisting indications for chronic anticoagulant treatment, based on the analysis of the real-world database. Methods Real-world data from the THIN database were analyzed. The population included adult patients from France and Great Britain undergoing CABG between 2010 and 2022 who were treated with anticoagulants within a year after CABG and who were followed for at least one year after CABG or until death. The endpoints were compared between groups of patients treated with anticoagulants in monotherapy (VKA or NOAC) (MT) and patients treated with anticoagulants (VKA or NOAC) in combination with antiplatelet agent (ASA or oral P2Y12 inhibitor) (CT). The primary efficacy endpoint was the occurrence of major adverse cardiac events (MACE), the primary safety endpoint was major bleeding and the secondary safety endpoint was death from any cause. Results A database query obtained records of 3500 patients meeting the inclusion criteria, but due to missing data, 710 patients were included in the analysis. In this group, 193 (27.2%) patients were in MT group, and 517 (72.8%) in CT group. The majority (87.0%) were men, the mean age was 72.8 (9.4) years. The MACE occurred in 19.2% patients in the MT and in 19.3% in the CT. There was no significant effect of antithrombotic treatment strategy on time to event (log-rank test p=0.553) and on risk of MACE occurrence (HR 0.89 (95% CI 0.61 - 1.31) for CT vs. MT). The major bleeding occurred in 6.2% patients in the MT and in 10.3% in the CT and no significant effect of group was observed (log-rank test p=0.170, HR 1.55 [95% CI 0.83 - 2.90] for CT vs. MT). The death from any cause occurred in 10.9% patients in the MT and in 10.1% in the CT and no significant effect of group was observed (log-rank test p=0.174, HR 0.70 [95% CI 0.42 - 1.17] for CT vs. MT). Conclusions The results indicate the comparable efficacy and safety of both antithrombotic treatment strategies: anticoagulants in monotherapy versus anticoagulants in combination with antiplatelet agent in the group of patients after CABG with coexisting indications for chronic anticoagulation.