Background: Recent studies have shown that the two major forms of multiple sclerosis are different in the degree of demyelination and atrophy, degree of inflammation, and extent of axonal loss. However, the majority of the previous studies that compared primary progressive and secondary progressive multiple sclerosis were carried out at the brain level. Material and methods: Human post-mortem spinal cords were used to compare the two progressive subtypes. In this project, the 5 major pathological changes associated with MS were studied in the spinal cords of primary progressive and secondary progressive multiple sclerosis. These changes include degree of demyelination, atrophy of the tissue, oligodendrocytes pathology, axonal loss, and neuronal pathology. Results: There was significant atrophy in the spinal cords of MS compared to healthy controls, which affects mainly the upper cord levels. There is a greater degree of demyelination and atrophy affecting secondary progressive compared to primary progressive especially in the upper cord levels. Oligodendrocytes numbers are dramatically reduced in the chronic lesions of WM and GM lesions. But there was high numbers of oligodendrocytes in the normally appearing GM of secondary progressive multiple sclerosis. There was greater reduction in axonal density in the secondary progressive sample especially in the normally appearing WM. Neurons were reduced in the demyelinated grey matter regions with no difference between the two disease forms in this respect. Conclusions: SPMS seem to have greater degree of tissue destruction in the form of demyelination, atrophy, and axonal loss in the normally appearing WM. However, SPMS showed greater numbers of oligodendrocytes in the demyelinated areas of the WM and the GM. Although the disability scale in the two examined groups was found to be similar, the tissue damage appeared to be variable.