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Background About 10% of patients undergoing cardiac surgery have a history of atrial fibrillation (AF). Among these patients, uncertainty exists regarding the safest and most effective oral anticoagulant (OAC) during the postoperative period. Purpose To evaluate practice patterns regarding OAC early after cardiac surgery in patients with a preoperative history of AF and to compare the safety and effectiveness of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Methods We conducted a nested cohort study within the Left Atrial Appendage Occlusion Study (LAAOS) III (NCT01561651). LAAOS III included patients with AF undergoing cardiac surgery with a CHA2DS2-VASC ≥2. In this substudy, we examined patients without end-stage renal dysfunction (eGFR >30 mL/min/1.73m2) who were discharged on OAC. We evaluated bleeding and thromboembolism within 90 days postoperatively using logistic regression adjusting for CHA2DS2-VASC score. Results Recruitment started in 2012 and completed in 2018 in 113 centres in 31 countries. Of the 4811 patients enrolled in LAAOS III, 3725 (77%) were included in this substudy. Preoperatively, 58% of patients received OAC: 56% DOACs and 44% VKAs. At hospital discharge 23% received DOACs and 77% VKAs; 55% of patients on a DOAC at baseline were switched to a VKA while 5% of patients on a VKA were switched to a DOAC. Patients discharged on a DOAC were older, had a higher CHA2DS2-VASC, and were more likely to be male. Patients having undergone an isolated coronary bypass procedure were more likely prescribed DOACs than VKAs (41% vs 23%, p Conclusions VKAs was the dominant OAC used early after cardiac surgery, but postoperative OAC practices varied by region. After adjustment for CHA2DS2-VASC score, the early postoperative incidence of major bleeding and of the composite of stroke and systemic arterial embolism did not differ significantly when DOACs were compared with VKAs. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): CIHR, Heart and Stroke Foundation