PURPOSE: To evaluate the integrity of the photoreceptor inner segment/outer segment (IS/OS) junction using spectral-domain optical coherence tomography (SD OCT) in patients with diabetic macular edema and to correlate the relationship between the integrity of the IS/OS junction and visual acuity. DESIGN: Retrospective, comparative, consecutive case series. METHODS: Sixty-two eyes from 38 patients with diabetic macular edema underwent SD OCT imaging. For each patient, 2 experienced observers masked to visual acuity measured several SD OCT variables, including central macular thickness, retinal volume, global disruption scale of outer retina, percentage disruption of the outer retina, and history of previous treatments. Visual acuity recorded as number of Early Treatment Diabetic Retinopathy Study letters was used as the outcome variable in univariate and multivariate analysis testing the measured SD OCT variables as predictors. RESULTS: A statistically significant correlation between percentage disruption of the IS/OS junction and visual acuity was found (P = .0312). Additionally, there was a strong trend suggesting a relationship between macular volume and visual acuity, although borderline significance was found (P = .07). CONCLUSIONS: Disruption of the photoreceptor IS/OS junction is an important predictor of visual acuity among diabetic macular edema patients.