Motor disability in MS is commonly assessed by the Expanded Disability Status Scale (EDSS). Categorical rating scales are limited by subjective error and inter-rater variability. Therefore, objective and quantitative measures of motor disability may be useful to supplement the EDSS in the setting of clinical trials. It was previously shown that grip-force-variability (GFV) is increased in MS. We hypothesized that GFV may be an objective measure of motor disability in MS. To investigate whether the increase in GFV in MS is correlated to the clinical disability as assessed by the EDSS and to microstructural changes in the brain as assessed by diffusion tensor imaging, GFV was recorded in a grasping and lifting task in 27 MS patients and 23 controls using a grip-device equipped with a force transducer. The EDSS was assessed by neurologists experienced in MS. Patients underwent diffusion tensor imaging at 3T to assess the fractional anisotropy (FA) of the cerebral white matter as a measure of microstructural brain integrity. GFV was increased in MS and correlated to changes in the FA of white matter in the vicinity of the somatosensory and visual cortex. GFV also correlated with the EDSS. GFV may be a useful objective measure of motor dysfunction in MS linked to disability and structural changes in the brain. Our data suggests that GFV should be further explored as an objective measure of motor dysfunction in MS. It could supplement the EDSS, e.g., in proof of concept studies.