Purpose Apixaban, a direct oral anticoagulant is administered for stroke prevention in atrial fibrillation patients. Dosing adjustment is guided by renal function, age, and body weight. However, no data exist on its pharmacokinetics in patients with a body mass index (BMI) ≥ 35 kg/m². The aim was to investigate the effects of BMI ≥ 35 kg/m² on trough plasma concentrations of apixaban in patients with atrial fibrillation. Methods This prospective study compared steady-state trough concentrations of apixaban in patients with a BMI ≥ 35 kg/m² and patients with a BMI < 35 kg/m². Results Sixty patients were included. In patients receiving 5 mg apixaban twice daily, the median trough plasma concentration was 29% lower in patients with a BMI ≥ 35 kg/m² than in those with a BMI < 35 kg/m² (148.9 ng/ml, interquartile range [IQR] 94.5–205.6, compared to 209.1 ng/ml, IQR 167–266.8 ng/ml, respectively; P = 0.044). However, median trough concentrations fell within the manufacturer’s predicted range for effective steady-state apixaban exposure. A similar trend was observed with 2.5 mg apixaban twice daily, although statistical significance was not reached. Multivariate analysis revealed no correlation between BMI values and trough concentrations. Conclusion BMI ≥ 35 kg/m² patients exhibited lower apixaban trough concentrations, while remaining within the manufacturer’s established range for effective steady-state apixaban, suggesting that dose adjustment is unnecessary for this specific patient group.