Retrovirus-like particles containing the multiple sclerosis-associated retrovirus RNA, significantly found in the cerebrospinal fluid of patients with multiple sclerosis, have been preliminarily associated with a short-term poor clinical and radiological prognosis of the disease. We asked whether these prognostic indications are still measurable after a long-term clinical evaluation (10 years). Our 10-year blind observational study confirms that the presence of multiple sclerosis-associated retrovirus in the cerebrospinal fluid of early multiple sclerosis patients is associated with a significantly greater rate of relapse-unrelated unremitting disability and secondary progression of the disease.