Background: Neuro-Behcet’s disease (NBD) is similar to multiple sclerosis (MS) in multiple aspects. This study was conducted to investigate the sensitivity, specificity, accuracy, positive and negative predictive values for the 2005 revised McDonald MRI criteria for the diagnosis of MS and NBD. Methods: This study enrolled 28 consecutive patients with a diagnosis of NBD and 48 patients with a diagnosis of clinically definite MS, who were referred to the Nemazee Hospital, Shiraz University of Medical Sciences, between March 2009 and March 2010. Brain and spinal cord magnetic resonance imaging (MRI) were obtained. Two Radiologists, blinded to clinical diagnosis, reviewed the MRI. We investigated the sensitivity, specificity, accuracy, and positive and negative predictive values of the 2005 revision of the McDonald criteria for dissemination in space for the diagnosis of MS and NBD. Results: There were a total of 10 men and 38 women with a mean age of 32.76±7.5 years, with a diagnosis of MS, and 18 men and 10 women with a mean age of 26.8±5.9 years with a diagnosis of parenchymal NBD. The interobserver agreement for the diagnosis of MS using the 2005 revision of the McDonald criteria for dissemination in space with the use of the Cohen kappa scores was 0.82. The sensitivity, specificity, accuracy, and positive and negative predictive values were 80%, 61%, 71.5%, 77% and 64%, respectively. Conclusion: The accuracy and specificity of the McDonald criteria for dissemination in space for the differentiation of MS and NBD are not optimal.