Shoulder pain and the resultant dysfunction is an expected problem in individuals with spinal cord injury. But there is a remarkable lack of information about the natural history, diagnosis, prevention and long term outcomes. Degenerative changes may develop prematurely in their shoulders, due to overuse and altered mechanical stresses, with or without symptoms was the hypothesis of this prospective study. Information from this study is expected to assist in identification of high risk SCI individuals, and ultimately in development of preventive strategies. The shoulders of 53 spinal cord injury patients from the onset of injury until 15 years duration were subjected to clinical and radiological examination at the Rehabilitation Institute of Chicago. Thirty-eight out of 53 (72%) patients demonstrated radiological evidence of degenerative changes, but only six (11%) complained of pain in the shoulders. This study demonstrated a correlation between individuals with higher level of wheelchair activity (72%), higher age (92% above and 8% less than 30 years) and female gender (89% females versus 65% males) more prone to develop degenerative changes in the shoulders. Acromioclavicular joint was predominantly affected. Detailed radiological findings, etiopathological factors and long term recommendations are discussed. The need for further studies and consistent management strategies are stressed.