Objective: To explore sensitivity of optical coherence tomography (OCT) in detecting prior unilateral optic neuritis. Methods: Retrospective, observational clinical study of all patients who presented from 1/1/14 to 6/1/17 with unilateral optic neuritis and OCT available at least three months after the attack. We compared OCT retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thicknesses between affected and unaffected contralateral eyes. We excluded patients with concomitant glaucoma or other optic neuropathies. Based on analysis of normal controls, thinning was considered significant if RNFL was at least 9-µm or GCIPL was at least 6-µm less in affected eye compared to unaffected eye. Results: Fifty-one patients (18 male and 33 female) were included in the study. RNFL and GCIPL thicknesses were significantly lower in eyes with optic neuritis compared to unaffected eyes (p<0.001). RNFL was thinner by ≥9-µm in 73% of optic neuritis eyes compared to the unaffected eye. GCIPL was thinner by ≥6-µm in 96% of optic neuritis eyes. The sensitivity of OCT in detecting prior optic neuritis was 96% when using both average RNFL and GCIPL thicknesses. When using a threshold ≤1st percentile of age-matched controls, sensitivities were 37% for RNFL, 76% for GCIPL, and 78% for either GCIPL or RNFL thicknesses, each of which was lower than those calculated using the inter-eye difference as the threshold (p<0.05). Conclusions: OCT, especially in GCIPL, is a highly sensitive modality in detecting prior optic neuritis, which is made more robust by using inter-eye differences to approximate change.