Because the development of new treatments in multiple sclerosis as well as the awareness of the importance of patient-oriented measures have become more important in the last two decades, new outcome measures have been developed with the aim of being more responsive to change and more clinically relevant to patients. The ability to detect improvement is sparsely studied. In the present study we evaluate the responsiveness of the Expanded Disability Status Scale and two quantitative tests (the timed 25-foot walk test and the nine-hole peg test) separately and in combination, to detect improvement after intravenous methylprednisolone. The Expanded Disability Status Scale, the timed 25-foot walk test and the nine-hole peg test were assessed in 112 multiple sclerosis patients before and 6 weeks after intravenous methylprednisolone. In addition patients were asked to rate their change as an anchor to evaluate the performance of the tests. Combining the timed 25-foot walk test and the nine-hole peg test turned out to be the optimal combination of measures to predict patient perceived improvement (positive predictive value of 67% and a negative predictive value of 59%, likelihood ratio of positive test 2.31 (95% confidence interval 1.08-4.95)). In the higher Expanded Disability Status Scale range (4.5 and higher), for all measures a significant change was more often perceived as clinically relevant than in the lower disability range. The Expanded Disability Status Scale seems not to be the preferred outcome of choice to detect patient perceived improvement in multiple sclerosis, especially in the lower Expanded Disability Status Scale range. Combining the timed walk test and the nine-hole peg test can improve the sensitivity to detect clinically relevant changes without conceding with respect to specificity.