Background Magnetic resonance imaging is regarded as one of the most important markers for multiple sclerosis. It can detect lesions in order to establish dissemination in time and space, which would aid in the diagnosis. Two-dimensional FLAIR is a standard sequence in MS routine imaging because it suppresses cerebrospinal fluid signal, increasing contrast between lesions and CSF and improving white matter lesion detection. Newer 3D FLAIR sequences are expected to offer even more benefits, such as improved MS lesions detection and higher resolution due to thinner slice thickness. We aimed to compare the role of 3D Cube FLAIR imaging (versus standard 2D FLAIR) in the assessment of white matter lesions in MS patients, as well as to test the convenience of using maximum intensity projection (MIP) on 3D FLAIR images for faster and easier evaluation. Results This study included 160 MS patients. A 1.5 T routine brain MRI scan was performed, which included a 2D FLAIR sequence, followed by a 3D-FLAIR sequence. All images were analyzed after 3D-FLAIR images were reformatted into axial MIP images. Lesions were counted in each sequence and classified into supra-tentorial (periventricular, deep white matter, and juxta-cortical), and infra-tentorial lesions, with the relative comparison of lesions numbers on 3D-FLAIR and MIP versus 2D-FLAIR expressed as a percentage increase or decrease. 3D FLAIR can significantly improve MS lesion detection in all areas of the brain when compared with 2D FLAIR results. At 2 mm reformatting, there is no difference in MS lesion detection between sagittal 3D FLAIR and axial MIP reconstruction, implying that the MIP algorithm can be used to simplify lesion detection by reducing the number of images while maintaining the same level of reliability. Conclusion 3D FLAIR sequences should be added to conventional 2D FLAIR sequences in the MRI protocol when MS is suspected.