Double diffusion encoding (DDE) measurements of microscopic anisotropy show promise as a method of assessing neurodegeneration. Unfortunately, DDE has yet to be demonstrated in a clinical setting due to constraints in SNR and scan time. Here, we used an optimized gradient orientation scheme to show the first DDE measurements of microscopic anisotropy in multiple sclerosis (MS) patients. Five MS patients were scanned using a DDE sequence optimized to run in five minutes. The microscopic anisotropy maps show improved visualization of axonal damage compared to fractional anisotropy (FA) and may provide additional insight into changes in tissue microstructure.