Objective: To examine the relationship between early response to anti-vascular endothelial growth factor (VEGF) treatment and visual prognosis. Methods: We retrospectively separated 20 patients with persistent diabetic macular edema (DME) into two responder status groups based on the reduction of central macular thickness (CMT) from baseline to month 3: a delayed responder group (DRG) (≤25% CMT reduction, n = 11) and an immediate responder group (IRG) (>25% CMT reduction, n = 14). We also separated the patients into two responder status groups based on the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA): a visual nonimprovement group (VNIG) (≥0 logMAR BCVA improvement, n = 11) and a vi sual improvement group (VIG) (<0 logMAR BCVA improvement, n = 14). Finally, we assessed the correlations between logMAR BCVA changes from baseline to month 3 (ΔBCVAM3) and those from baseline to month 12 (ΔBCVAM12). Results: At month 12, BCVA was significantly more improved in the VIG than the VNIG (p < 0.005), but was not significantly different between the DRG and the IRG (p = 0.75). The Pearson correlation coefficient showed a significant relationship between ΔBCVAM3 and ΔBCVAM12 (r = 0.60, p < 0.005). Conclusions: BCVA showed significantly greater improvement in the VIG than in the VNIG. ΔBCVAM3 may predict the visual outcome at month 12 in DME patients treated with anti-VEGF drugs.