We aimed to evaluate the long-term (>2 years) outcome of acute and subacute myelopathies (ASM). We systematically followed-up consecutive patients presenting with a first episode of ASM, defined by spinal cord symptoms with an onset <3 weeks and duration ≥48 h. Patients with compressive or traumatic spinal cord lesions are excluded from this report. Our cohort consisted of 170 patients (median age 39.0 years, median duration of follow-up 73.2 months). The death rate was 8.8%, Lipton and Teasdall's functional score was bad or fair in 38.2%, and 37.1% of the survivors who worked when the ASM occurred were unable to carry on with the same profession. Unfavorable functional outcome was more frequent when (1) symptoms were initially severe, (2) the lesion was located centrally on spinal cord MRI and (3) the etiology was neuromyelitis optica (NMO) or systemic disease (SD). In one-third of patients the etiology at the end of follow-up differed from the etiology suspected after the initial diagnostic workup. Over half of patients initially diagnosed with myelopathy of undetermined cause subsequently developed multiple sclerosis, NMO or SD. ASM is a severe condition with a bad or fair functional outcome and a major impact on professional activity in one-third of the patients. Central lesions on spinal cord MRI and etiologies such as NMO or SD are associated with a worse functional outcome. Finally, a long-term follow-up is important given the large number of causes that are identified at a distance from the initial event.