Introduction: Brain derived neurotrophic factor (BDNF) played a role in neuroplasticity and was involved in several autoimmune diseases including multiple sclerosis (MS). Val66Met polymorphism affects BDNF secretion and needs more research to determine its impact. Our work aimed at evaluating the role of this polymorphism on motor disability and cognition in MS patients. Methods: This is a case control study involving 100 subjects (50 MS patients, 50 controls). A genetic testing for BDNF Val66Met and a thorough neuropsychological evaluation using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in the approved Arabic version were performed for all subjects. Progressive clinical disability measurement by the Expanded Disability Status Scale (EDSS) along with the Multiple Sclerosis Severity Scale (MSSS) were done for MS patients. Results: MS patients with the Met allele variant had longer course duration (P=0.009). Val/Val genotype patients had significantly more frequent relapses (P=0.017). Met carrier patients showed lower scores on all subtests of BICAMS but only reached a statistically significant difference in the Symbol digit modality test (SDMT) (P=0.04). In the logistic regression analysis for factors predicting disability, BDNF Val66Met polymorphism was not associated with disease disability. More frequent relapses, presence of high lesion load and cervical lesions on MRI brain could predict increasing disability on multivariate analysis. Conclusion: MS patients having met allele of the BDNF gene had significant cognitive dysfunction on the SDMT. However, our results could not suggest a significant effect of this polymorphism on other subtests of BICAMS neither on the clinical disability.