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Background: Grey matter involvement is suggested to have a role in pathophysiology of multiple sclerosis (MS). Objective: Our aim is to detect the thalamic involvement using 1.5 Tesla Diffusion tensor imaging (DTI) and its relationship with cognitive impairment, clinical disability and fatigue in MS patients. Methods: 31 patients with MS (23 RRMS and 8 SPMS) with mean age 34.4±8.5 SD were studied. We recruited also 18 age, sex and education level matched healthy controls. They all underwent clinical assessment, cognitive assessment using California verbal learning test, brief visuospatial memory test, paced auditory serial addition task (PASAT), symbol digit modalities test, controlled oral word association test, assessment of fatigue using fatigue severity scale, and radiological assessment using 1.5 T DTI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured over regions of interest over the thalamus. Results: Patients with MS had higher thalamic FA (P<0.01) and ADC (P<0.01) than controls. Patients showed significantly worse performance in all cognitive tests than controls. There was significant correlation between total EDSS and mean thalamic FA. In addition, there were good positive correlations between disease duration, number of attacks and mean FA over the thalamus. There were significant correlations between performance in neuropsychological tests, disease duration, number of attacks and total EDSS. Conclusion: DTI was able to detect abnormalities in normal-appearing thalamus of patients with MS. Thalamic involvement had significant relations with cognitive impairment and clinical disability in patients with MS. [ABSTRACT FROM AUTHOR]