We evaluated clinical presentation, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) in patients with late-onset multiple sclerosis (LOMS). Fifty-two patients with definitive multiple sclerosis (MS) diagnosed after the age of 50 years were identified between 1991 and 2002. Data pertaining to clinical characteristics, CSF analysis, and cerebral and spinal MRI were compared with those of 52 young-onset MS (YOMS) patients matched for sex and disease duration. Mean age at the time of diagnosis was 57 years in the LOMS group - the oldest patient was 82 - and 29 years in the YOMS group. Motor symptoms were significantly more often present in the LOMS than in patients with YOMS (90 % vs. 67 %, p = 0.014). Visual symptoms, residual signs of optic neuritis, and dysarthria were less frequent for LOMS. Sensory symptoms, ataxia, oculomotor symptoms, cognitive disorder, or fatigue did not differ between both groups. The majority of LOMS patients (83 %) had a primary progressive disease course, whereas 94 % of the YOMS group had a relapsing-remitting course. MRI showed typical multifocal supratentorial (LOMS vs. YOMS: 96 % vs. 98 %) and infratentorial (44 % vs. 62 %) lesions without significant group differences. Of particular interest, spinal lesions were more common (81 %) in LOMS compared to YOMS (48 %, p = 0.024), and cerebellar lesions were less frequent in the LOMS group (11 % vs. 44 %, p = 0.001). Gadolinium-enhanced lesions were initially present in less LOMS patients (15 %) than in YOMS (63 %, p < 0.001). CSF analysis revealed pleocytosis less frequently in LOMS (34 %) compared to YOMS (67 %, p = 0.006) but oligoclonal banding occurred without in both groups without differences. YOMS patients responded to corticosteroids (93 %) to a significantly greater degree than LOMS patients (73 %; p = 0.004). For individuals who develop LOMS, a primary progressive course is frequent, with motor symptoms as the prominent feature. Vigilance is necessary to recognise MS in this population because of its unusual presentation.