Background: It is widely accepted that multiple sclerosis effect on white matter extends beyond the demyelinating plaques and that the apparent diffusion coefficient (ADC) measurement can offer an insight on the effect of multiple sclerosis on normal appearing white matter. Objective: The aim of the current work was to evaluate the role of ADC in assessment and follow up of multiple sclerosis patients. Patients and Methods: This retrospective study included a total of 20 healthy volunteers and 50 multiple sclerosis patients in different clinical subtypes, referred from Neurology Department and Outpatient Clinics, and conducted at Department of Radiodiagnosis, Ain Shams University Hospital. A follow up Magnetic resonance imaging (MRI) with ADC measurement was done every 6 months for 3 years. Results: There was significant difference in the ADC of the normal appearing white matter of normal individuals and multiple sclerosis patients (P<0.0001). There was also significant difference in ADC measurement of plaques between relapsing remittent and chronic progressive cases (P<0.0001). The cutoff point in differentiating normal from multiple sclerosis patients was 0.8 ×10−3mm2/sec with sensitivity 93.7%, specifity94.3% and accuracy 85%. The cutoff point in differentiating relapsing remittent cases from progressive cases was 1.3 ×10−3mm2/sec with sensitivity 89.3%, specificity 85% and accuracy 80%. Conclusion: It could be concluded that routine measurement of the ADC value of the normal appearing white matter and multiple sclerosis plaques can help in assessment of the clinical subtype and shows high correlation with the degree of the disease progression.