Background and purpose: Increasing evidence suggests the presence of demyelination in the normal-appearing white matter (NAWM) of patients with neuromyelitis optica spectrum disorder (NMOSD). The objective was to determine the presence of subclinical demyelination in the NAWM of patients with NMOSD using myelin water imaging (MWI). Methods: Whole brain and regions-of-interest (ROIs) analyses, including the centrum semiovale, corona radiata, genu and splenium of the corpus callosum, and optic radiation, were conducted in the NAWM of 28 NMOSD patients and 18 healthy controls (HCs) using two MWI modalities: conventional MWI and direct visualization of short transverse relaxation time component (ViSTa) MWI. Results: Conventional myelin water fractions (MWFs) of the global NAWM and three ROIs (centrum semiovale, corona radiata, and genu of the corpus callosum) were slightly lower in NMOSD patients than in HCs, although not statistically significant. On the other hand, ViSTa MWF values of the global NAWM and all ROIs except the genu of the corpus callosum were significantly lower in NMOSD patients relative to HCs. In particular, the MWF in the optic radiation was significantly reduced in NMOSD patients relative to HCs in both MWI methods, even in patients who had no brain involvement. Additionally, patients with optic neuritis showed lower MWF than patients without optic neuritis and a negative correlation was identified between the MWF of the optic radiation and visual functional system score. Conclusions: This study identified the presence of widespread demyelination in the NAWM of NMOSD patients and highlighted the optic radiation as a site of marked demyelination.