Objective: To determine the course of daily functioning in patients with multiple sclerosis in the 10 years after their definite diagnosis. Methods: A long-term prospective follow-up study including an incidence cohort of 156 patients with multiple sclerosis. Participants were examined systematically, beginning immediately after definite diagnosis, then at the following timepoints: 6 months, 1, 2, 3, 6 and 10 years. The various domains of daily functioning were assessed with the Expanded Disability Status Scale, the Functional Independence Measure, and the Medical Outcome Study Short Form-36 (SF-36). Results: Neurological disability and physical functioning worsened significantly, with a time course dependent on whether a patient had multiple sclerosis of the relapse onset type or non-relapse onset type. Cognitive and social functioning worsened significantly over time, but with the same (accelerated) rate of change in both the RO and NRO groups. Scores on SF-36 mental health, SF-36 role physical, and SF-36 general health changed only slightly. Conclusion: In the first 10 years after definite diagnosis, patients with multiple sclerosis showed a more pronounced decline in physical functioning than in cognitive and social functioning. There was no time-related decline in mental health, social role due to physical limitations, or general health. © 2013 The Authors.