This study aims to compare clopidogrel and rivaroxaban against ischemia-reperfusion injury after a long reperfusion time and to investigate its effects on various tissues.A total of 40 Wistar rats were included in the study and were randomly divided into four groups (n=10 per group). Groups were defined as follows: control (Group 1), sham (Group 2), clopidogrel pre-treatment (Group 3), and rivaroxaban pre-treatment (Group 4). Ischemia (6 h) and reperfusion (8 h) were induced at the lower hind limb in Groups 2, 3, and 4. The ischemic muscle, heart, kidney, liver, and plasma tissues of the subjects were obtained to test for the oxidant (malondialdehyde) and antioxidants (glutathione, superoxide dismutase, and nitric oxide).Malondialdehyde levels were significantly higher in the sham group, compared to the controls in all tissues. Clopidogrel and rivaroxaban pre-treatment significantly decreased malondialdehyde levels, compared to the heart, ischemic muscle, liver, and blood tissues of the sham group. Kidney malondialdehyde levels were reduced only by rivaroxaban. Group 4 had significantly decreased malondialdehyde levels, compared to Group 3 in ischemic muscle (p<0.010). The glutathione reduction, compared to sham group, in the kidney was only significant for Group 4 (p<0.050). With clopidogrel and rivaroxaban pretreatment, nitric oxide levels significantly decreased only in the heart tissue, compared to sham group (p<0.001 and p<0.050, respectively).The study results suggest that rivaroxaban and clopidogrel are effective in reducing ischemia-reperfusion injury in the heart, ischemic muscle, liver, and blood. Rivaroxaban also protects the kidneys and is superior to clopidogrel in ischemic muscle protection.