Intrathecal IgM synthesis (ITMS) predicts a worse evolution in the first stages of multiple sclerosis (MS). The aim of this study was the follow-up of a group of relapsing-remitting MS patients for a longer time to evaluate whether the ITMS implies a poor prognosis. Oligoclonal IgM bands were performed in 29 MS patients followed up from 5 to 16 years. Time to conversion to secondary-progressive MS (SPMS), time elapsed to reach a disability of 6 in the Expanded Disability Status Scale (EDSS), percentage of patients with a benign MS, and changes in EDSS score were evaluated. During the follow-up, 70.8% of patients with ITMS converted to SPMS. None of the patients without ITMS did. At the end of the study, 63.6% of patients with ITMS had reached EDSS 6, whereas none of the patients lacking ITMS reached values above EDSS 3. When patients with benign MS were analyzed, 82% lacked ITMS. All patients with a nonbenign MS had ITMS. At the end of the study, the mean EDSS score was 4.64 in patients with ITMS and 1.31 in those without. The presence of oligoclonal IgM bands in cerebrospinal fluid is an unfavorable prognostic marker in MS.