Objective: The epigastric artery perforator flap is commonly used in the breast reconstruction. Ischemia during surgery results in the necrosis of the flap. We aimed to study the effect of fondaparinux in reperfusion injury in perforator flap model and determined its effects on the flap viability. Materials and Methods: Twenty-eight female Wistar Albino rats were included in this study. Rats were separated into three groups: A control (n = 9), B ischemia (n = 9), and C ischemia + drug (n = 10). Superior epigastric artery perforator flap on the single perforator was elevated in all groups. In Group A, flap was sutured back. In Group B, ischemia was applied for 4 h to the pedicle. In Group C, fondaparinux was administered 30 min before the reperfusion of the flap. Serum malondialdehyde (MDA), myeloperoxidase (MPO) levels, and histopathological examination of the flaps were studied. Results: The mean survival areas of flaps were 92.5%, 50.1%, and 91.1% in Group A, Group B, and Group C, respectively. Statistical differences were observed between these values (P < 0.05). The means of MPO and MDA were 22.3 ng/ml and 4.5 nmol/ml; 31.1 ng/ml and 4.7 nmol/ml; 27.1 ng/ml and 4.5 nmol/ml, respectively, for Group A, Group B, and Group C, and no statistically significant difference was found between groups (P > 0.05). Histopathologically, statistically significant difference was found between Group A, Group B, and Group C in terms of the infiltration of the leukocytes with polymorph nuclei (PMNL) for 24 h (P < 0.05). In the histopathological examinations done at the 7(th) day, statistically significant difference was found between groups in terms of edema, necrosis, increase in connective tissue, and leukocytes with polymorph nuclei (PMNL) (P < 0.05). Conclusion: Administration of fondaparinux after ischemia increased the flap viability in the epigastric artery perforator flap model.