Impairment of cognitive skills is found in up to 65% of patients suffering from multiple sclerosis (MS). Little is known concerning the natural history or characteristics of progression of these cognitive dysfunctions. Furthermore, it has not been investigated to date whether there are differences in the course of cognitive impairment with respect to different diagnostic subgroups of MS. Event-related potentials (ERP) are an objective tool to evaluate cognitive processing. We performed a cross-sectional study on 179 consecutive patients suffering from MS (107 relapsing-remitting MS; 17 primary progressive MS; 50 secondary progressive MS; 5 undetermined). ERP were measured by a visual oddball paradigm, latencies of P3 components were correlated with demographic and clinical data. We found pathologically increased P3 latencies in 56% of all patients. Patients with secondary progressive MS showed significantly increased P3 latencies as compared to the other subgroups. There was a significant correlation between expanded disability status scale (EDSS) score and P3 latency (r=0.48; p<0.001). We conclude that ERP are an appropriate method to follow up cognitive dysfunction in MS and that cognitive dysfunction as measured by ERP is progressively impaired in the course of MS, in particular in the secondary progressive subtype.