Introduction: Cognitive impairment occurs in a substantial number of multiple sclerosis (MS) patients and often includes frontal lobe dysfunction. We used functional magnetic resonance imaging (fMRI) to study planning, an executive function, in moderately impaired MS patients. Methods: An fMRI version of the Tower of London (ToL) test was used to study patterns of brain activation in 23 MS patients and 18 healthy controls. The median score on the Expanded Disability Status Scale (EDSS) for the MS patients was 4. fMRI data were analysed using whole brain random effects analysis as well as region of interest (ROI)-based methods to assess group effects. Within the MS group, associations with behavioural data and measures of disease severity (lesion load from structural MRI) were examined. Results: Test performance in MS patients was significantly worse than in controls. Group analysis for the MS patients and the controls showed for both groups globally the same areas of activation, located in the frontal and parietal lobes bilaterally and the cerebellum. Although visual inspection suggested a larger extent of activation in the MS group, no statistically significant differences between groups were found. In the ROI analysis, statistically significant larger extent of activation was only found in the cerebellum. No association between disease severity and brain activity could be determined in the MS group. Conclusion: In MS patients with moderate disability and structural damage, the pattern and extent of brain activation during planning were maintained despite poorer performance. In contrast to other studies showing increased activity, the failure to do so in our group may reflect exhaustion of adaptive mechanisms.