The neurological severity of a spinal cord injury (SCI) is commonly classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS). The aim of this study was to assess the course of the AIS following SCI, and to discern the nature of any changes in the classification that occur. Assessments were performed in a European cohort of SCI patients within 2 weeks and at 1, 3, 6, and 12 months after the initial injury. Overall, about 70% of the patients initially diagnosed as AIS A did not convert, as did 90% of the AIS D patients. When only evaluating patients with complete datasets, 68% did not convert, while the AIS category improved in 30% of patients and deteriorated in 2%. A change in the last sacral segments (40%), motor improvement (31%), sensory improvement (19%), and a change in the neurological level of the SCI (10%) contributed to or accompanied the AIS conversion. When the AIS remained unchanged between successive assessment points, there was no change in the number of muscles graded three or more (NMG3(+)) in 73% of the transitions. An improvement in AIS was associated with a gain in NMG3(+) in 49% of the transitions, while an aggravation in AIS was accompanied by a loss in NMG3(+) in 10% of the transitions. These results, documenting a substantial amount of spontaneous AIS conversions, should be taken into consideration when designing clinical trials to assess the effects of potential new treatments for SCI.