Abstract To elucidate the mechanisms influencing visual function recovery after optic neuritis (ON), this study employed a multicompartment diffusion weighted imaging (DWI) model to assess the role of optic radiation integrity and its relationship with retinal parameters, including automatic retinal oximetry and retinal nerve fiber layer (RNFL) thinning. Twenty-four patients with the first episode of acute unilateral ON were compared with 56 healthy volunteers with normal vision. Additionally, longitudinal analysis 3 and 6 months after ON was performed in 17 patients. Multivariate analysis of variance across baseline DWI metrics revealed a greater secondary partial volume fraction (f2) in patients. In the longitudinal analysis, a multivariate effect of time was observed only when adjusted for the affected side and time since onset; however, univariate post hoc tests were nonsignificant. An unadjusted model stratified according to clinical outcomes (best-corrected visual acuity [BCVA] and contrast sensitivity) indicated lower overall fractional anisotropy (FA) in patients with incomplete recovery. In the correlation analysis, baseline FA and oximetry (venous saturation and arteriovenous difference) predicted follow-up BCVA, whereas axial diffusivity predicted follow-up oximetry. In turn, baseline oximetry predicted follow-up RNFL thickness. In summary, DWI and retinal oximetry are both potential predictors of visual function outcomes after ON.