Eleven consecutive patients with a first episode of acute optic neuritis were evaluated, using conventional and magnetization transfer (MT) magnetic resonance imaging (MRI), in order to assess the temporal evolution of optic nerve (ON) damage and to investigate the correlation of ON damage with visual outcome and electrophysiological parameters. Patients underwent neuroophthalmological, neurological, electrophysiological, and MRI assessments at baseline and after three and 12 months. ON volumes were measured on coronal T1-weighted images using a local thresholding segmentation technique. MT ratio (MTR) from the ON was derived from gradient echo images. No significant volume difference was detected between affected and healthy ON, both at baseline and follow-up. At baseline, mean MTR values were significantly higher in affected ON than in healthy ON (P =0.001), whereas at months 3 and 12, the mean MTR values were significantly reduced in the affected ON (P =0.02 and 0.003, respectively). Mean MTR of the affected ON, corrected for healthy ON values, progressively decreased over time (P =0.04 at month 3 and P =0.0012 at month 12). On the contrary, MTR values of healthy ON remained stable. No correlations were found between MTR measures and clinical or electrophysiological data. This study shows the presence of subtle pathological changes, possibly due to residual demyelination and subsequent additional demyelination and impaired remyelination, in the ON of patients with a first episode of optic neuritis. In the early phase of optic neuritis, MT MRI is more sensitive than atrophy measurements in detecting disease-related changes.