BACKGROUND AND OBJECTIVE: To assess the impact of the disorganization of retinal inner layers (DRIL) on visual acuity (VA) and its correlation with ischemic index (IsI) on ultra-widefield fluorescein angiography (UWFFA) in eyes with acute, treatment-naïve branch retinal vein occlusion (BRVO). PATIENTS AND METHODS: Retrospective, longitudinal study of BRVO eyes with 1 year of follow-up or more. Area of intraretinal cysts, DRIL length, extent of disruption of external limiting membrane (ELM), and ellipsoid zone (EZ) were graded on the central 1,000 μm of foveal optical coherence tomography (OCT) scan. Baseline IsI was calculated on UWFFA. RESULTS: Thirty eyes of 30 patients with a mean follow-up of 25.4 months ± 11.0 months were evaluated. At baseline, 50% had DRIL (mean 443.1 μm ± 460.4 μm). DRIL length at baseline was predictive of worse VA at 12 months (P = .029), and DRIL length at 12 months was predictive of worse final VA(P = .011). In multivariate analyses, DRIL length was associated with final VA (P = .008) after controlling for other OCT parameters. There was no association between baseline IsI on UWFFA and DRIL. CONCLUSIONS: DRIL served as an independent OCT biomarker predictive of worse VA during a period of 2 years in acute, treatment-naïve BRVO. Development of DRIL was influenced by presence of CME, intraretinal cyst area, and extent of ELM and EZ disruption, but not by severity of baseline IsI. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:354-364.].