OBJECTIVE Previous studies have shown niacin has neuroprotective effects on the central nervous system. However, its specific effect on spinal cord ischemia/reperfusion injury has not yet been explored. This study aims to evaluate whether niacin can contribute neuroprotective effects on spinal cord ischemia/reperfusion injury. METHODS Rabbits were randomized into 4 groups of 8 animals: group I (control), group II (ischemia), group III (30 mg/kg methylprednisolone, intraperitoneal), and group IV (500 mg/kg niacin, intraperitoneal). The rabbits in group IV were premedicated with niacin for 7 days prior to inducing ischemia/reperfusion injury. The control group was subjected only to a laparotomy, while the remaining groups underwent spinal cord ischemia through a 20-minute occlusion of the aorta caudal to the left renal artery. Following the procedure, levels of catalase, malondialdehyde, xanthine oxidase, myeloperoxidase, and caspase-3 were analyzed. Ultrastructural, histopathological, and neurological evaluations were also performed. RESULTS Spinal cord ischemia/reperfusion injury resulted in increased levels of xanthine oxidase, malondialdehyde, myeloperoxidase, and caspase-3, with a concomitant decrease in catalase levels. Treatment with methylprednisolone and niacin led to decreased levels of xanthine oxidase, malondialdehyde, myeloperoxidase, and caspase-3 and an increase in catalase. Both methylprednisolone and niacin treatments demonstrated improvements in histopathological, ultrastructural, and neurological assessments. CONCLUSIONS Our findings suggest that niacin has antiapoptotic, anti-inflammatory, antioxidant, and neuroprotective effects at least equal to methylprednisolone in ischemia/reperfusion injury of the spinal cord. This study is the first to report the neuroprotective impact of niacin on spinal cord ischemia/reperfusion injury. Further research is warranted to elucidate the role of niacin in this context.