Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that primarily affects the vertebral column and sacroiliac joints. Over time, the disease process promotes extensive remodeling of the spinal axis via ligamentous ossification, vertebral joint fusion, osteoporosis, and kyphosis. These pathological changes result in a weakened vertebral column with increased susceptibility to fractures and spinal cord injury (SCI). Spinal cord injury is often exacerbated by the highly unstable nature of vertebral column fractures in AS. A high incidence of missed fractures in the ankylosed spine as well as an increased incidence of spinal epidural hematoma also worsens the severity of SCI. Spinal cord injury in AS is a complex problem associated with high morbidity and mortality rates, which can be attributed to the severity of the injury, associated medical comorbidities, and the advanced age of most patients with AS who suffer an SCI. In this paper the authors outline the factors that increase the incidence of vertebral column fractures and SCI in AS and discuss the management of SCI in patients with AS. Primary prevention strategies for SCI in patients with AS are outlined as well.