We monitored disease progression in 27 patients with clinically or laboratory‐supported definite multiple sclerosis by means of clinical assessments [expanded disability status scale (EDSS), and the neurologic rating scale (NRS)] repeated at 6 month intervals for 2 years. Each clinical assessment was accompanied by evoked potentials (EP; visual, brain stem auditory, and somatosensory evoked potentials), motor evoked potentials elicited by magnetic stimulation, and magnetic resonance imaging of the brain and brain stem. Central conduction indices were calculated for each central pathway. According to the EDSS 18 patients deteriorated, eight were unchanged and one improved. The central motor conduction index (CMCI) was the only conduction parameter which correlated significantly with both EDSS and NRS at baseline [rho=0.51 (EDSS); ‐0.65 (NRS)], at final investigation, and when individual changes from baseline to final investigation were addressed (rho=0.38; ‐0.38). Individual deteriorations or improvements of the CMCI during the 2 years correlated with changes in both EDSS and NRS (rho = 0.51; ‐0.38). The MRI parameters did not correlate with the clinical scores. The concordance between MRI and CMCI in detection of disease activity was 63%. We conclude that the CMCI stands out as an objective, accurate and easily obtained outcome pa