Study Design.The effect of amlodipine (AM) on spinal cord injury (SCI) and autophagy was researched by establishing ventral spinal cord cells (VSC4.1) oxygen and glucose deprivation model and SCI mice model.Objective.To determine the neuroprotective effects of AM by upregulating autophagy during SCI repair.Summary of Background Data.AM, an antihypertensive medication, has been shown in several studies to inhibit neuronal apoptosis and exert neuroprotective effects in various central nervous system diseases. However, its effects on SCI are unexplored. Autophagy could inhibit cell apoptosis, which has been shown to promote SCI repair. However, the role of AM in autophagy remains unclear.Methods.We examined the relationship between AM, apoptosis, and autophagy in ventral spinal cord cells and the injured spinal cords of C57BL/6 female mice respectively, following histological, behavioral, microscopic, immunofluorescence, and western blotting analyses.Results.We found that AM could inhibit motor neuronal apoptosis in vitro. Furthermore, AM promoted locomotor recovery by upregulating autophagy and alleviating apoptosis, neuronal loss, and spinal cord damage after SCI.Conclusion.AM inhibited motoneuronal apoptosis by upregulating autophagy to improve SCI recovery.