Purpose: The Area Deprivation Index (ADI) is a validated composite measure of socioeconomic status (SES) in which higher percentiles correspond to lower SES. This study sought to assess differences in the use of anti–vascular endothelial growth factor (anti-VEGF) therapy and treatment response across national ADI scores in patients with diabetic macular edema (DME). Methods: This was a US single-center, retrospective review of patients diagnosed with DME between 2014 and 2022 and followed for up to 24 months after diagnosis. Primary outcomes were best-corrected visual acuity (BCVA), central foveal thickness (CFT), and macular volume (MV), measured at 6-month intervals from DME diagnosis. Patients were classified as either low ADI (higher SES) or high ADI (lower SES) using the 75th national ADI percentile. Results: The low ADI group comprised 60 patients, and the high ADI group comprised 57 patients. Baseline functional and anatomic characteristics were similar between groups. There were no significant treatment differences (type or number of anti-VEGF and steroid injections) between groups. After 24 months, mean BCVA was 0.82 logMAR (95% CI, 0.61–1.03) in the high ADI group and 0.51 logMAR (95% CI, 0.31–0.71) in the low ADI group (P = .03). Mean final CFT and MV were not significantly different between groups (P > .05); however, patients in the low ADI group were more likely to receive cataract surgery within the treatment period (P = .04). Conclusions: Socioeconomic disadvantage does not appear to influence anti-VEGF treatment patterns or anatomic outcomes in patients with DME. However, BCVA was significantly better in the low ADI group at the end of the 24-month study period. This finding may be due to socioeconomically advantaged patients being more likely to receive cataract surgery during the treatment period.