BACKGROUND: Rivaroxaban, a direct Factor Xa inhibitor, primarily acts by disrupting the coagulation cascade. However, it may also influence oxidative stress. This effect likely stems from its ability to reduce thrombin-mediated reactive oxygen species (ROS) production and mitigate inflammation. The major aim of the present investigation was to assess the effects of Rivaroxaban on oxidative stress and antioxidant capacity in patients with heart failure. METHODS: This study included 39 patients (17 males and 22 females, aged 30-95 years) with Stage B heart failure (HF) who had never previously received Rivaroxaban. Patients were enrolled from Chamran Cardiovascular Hospital in Isfahan after providing written informed consent, approved by the Falavarjan University Ethical Committee (IR.IAU.FALA.REC.1398.029). All patients had structural cardiac abnormalities, including reduced left ventricular ejection fraction (LVEF < 40%) or diastolic dysfunction, but no clinical symptoms of HF. Rivaroxaban (20 mg/day) was administered orally to all patients for two months using a pre-post design. Blood samples were collected before and after treatment to assess oxidative stress and antioxidant biomarkers, including total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (Hcy), and the enzymatic activities of paraoxonase-1 (PON1) and arylesterase. TAC, MDA, and enzyme activities were measured spectrophotometrically, while homocysteine levels were determined using ELISA. RESULTS: The results showed a significant reduction in MDA levels (P < 0.001), indicating reduced oxidative stress after Rivaroxaban treatment. However, no statistically significant changes were observed in other biomarkers, including homocysteine, arylesterase, paraoxonase, and TAC (P > 0.05). CONCLUSION: In conclusion, Rivaroxaban appears to effectively reduce oxidative stress, as evidenced by decreased MDA levels.