New-onset postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery, especially coronary artery bypass grafting (CABG), affecting up to 40% of patients, and is associated with increased risks of thromboembolic events and prolonged hospital stays. Traditionally, warfarin has been the standard anticoagulant for stroke prevention in atrial fibrillation. However, it requires regular international normalized ratio monitoring. Direct comparisons between apixaban and warfarin in the CABG population remain scarce. This study aimed to compare the effectiveness and safety of apixaban versus warfarin in patients with POAF after CABG. A retrospective observational cohort study was conducted at King Abdulaziz Medical City, Riyadh, from January 1, 2017, to December 31, 2023. Eligible patients aged 18 and older who developed new-onset POAF and received apixaban or warfarin within 7 days postsurgery were included. The primary outcome was the incidence of thromboembolic events, while the secondary outcomes were safety outcomes, including bleeding complications. Out of 1277 records, 143 patients met the inclusion criteria. The incidence of thromboembolic events within 90 days was slightly lower in the apixaban group (2.0%) compared to warfarin (7.0%), though not statistically significant (P = .137). Major bleeding events occurred in 6.0% of patients on apixaban and 7.0% on warfarin (P = .825), and minor bleeding rates were also not statistically different, with 7.0% for apixaban and 11.6% for warfarin (P = .360), indicating no difference in safety profiles. Apixaban and warfarin demonstrated similar efficacy in preventing thromboembolic events and comparable safety regarding bleeding complications in patients with POAF following CABG, supporting apixaban as a reasonable alternative in this population.