Background: Late-onset multiple sclerosis (LOMS), defined as symptom onset after age 50, poses unique diagnostic and management challenges. Despite increased recognition of LOMS globally, data on its clinical and demographic characteristics in Latin America remain scarce. This study describes the demographic, clinical, and paraclinical profile of LOMS patients in a Colombian reference center. Methods: We conducted an observational study nested within the MS patient registry at the National University Hospital of Colombia. Patients meeting the 2017 McDonald criteria with symptom onset after age 50 were included. Variables analyzed included demographic data, MS onset symptoms, phenotype, disability progression, comorbidities, and treatment patterns. Descriptive statistics were applied. Results: Of 596 MS patients, 39 (6.54 %) met LOMS criteria, with a mean age at onset of 54.6 years (SD: 5.12). The cohort was predominantly female (69.2 %). Motor symptoms were more common in men (66.7 %) and sensory symptoms in women (48.1 %). Relapsing-remitting MS (RRMS) was the most frequent phenotype (79.4 %). Median EDSS increased from 1.5 to 2.5 over a mean follow-up of 3.96 years. Hypertension (41 %) was the most common comorbidity. Most RRMS patients initiated low-efficacy disease-modifying treatments (DMTs), while high-efficacy DMTs were predominant in primary progressive MS cases. Conclusions: LOMS in this Colombian cohort aligns with global trends but highlights regional nuances, including a diagnostic delay and underutilization of high-efficacy therapies. These findings highlight the need for tailored diagnostic and therapeutic approaches to optimize outcomes for LOMS in low-prevalence regions.