Background: The aim of our work was to assess the diagnostic accuracy of a double inversion recovery (DIR) sequence in the detection of brain and spinal cord MS lesions. In addition, we aimed to evaluate the reliability of the correlation between GM affection and high Expanded Disability Status Scale (EDSS) to enhance the role of DIR as a practical test for clinical disability. Ninety MS patients were prospectively included in this study. Imaging was performed using Philips Intera 1.5 Tesla device. T2W-TSE, FLAIR, and DIR sequences were performed and compared to each other. Each patient was clinically assessed at the time of the MRI examination with EDSS. Results: DIR showed significantly higher total lesion load in comparison to T2 and FLAIR with increased sensitivity for cortical lesion detection by DIR. There was a positive association between patients with cortical lesions and male gender, clinical disability, cognitive changes, and higher EDSS score. Conclusion: The increased rate of cortical lesion detection by DIR does not affect its accuracy in white matter lesions count. Moreover, DIR provided a better morphological characterization and delineation of white matter lesion with good differentiation between juxtacortical and mixed white matter-gray matter lesions; thus, we recommend adding DIR sequence in routine MR protocols for MS patients.