Purpose: This study evaluates the effect of anti-vascular endothelial growth factor (anti-VEGF) therapy on microaneurysm changes and foveal avascular zone (FAZ) using optical coherence tomography angiography (OCTA) in patients with diabetic macular edema (DME). Design: Prospective observational study. Materials and Methods: This study involved patients with DME undergoing anti-VEGF treatment (aflibercept, ranibizumab, and bevacizumab). Macula OCTA images were obtained before (visit 0) and 1 month after (visit 1) anti-VEGF injection. Microaneurysm counts were performed, and the FAZ was evaluated in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The differences in microaneurysms, FAZ, and clinical correlations were analyzed. Results: A total of 152 eyes were analyzed. The patients’ mean age was 59 years. Bevacizumab was used in 69.7%, ranibizumab in 15.1%, and aflibercept in 15.1%. There was a significant reduction in the FAZ in the SCP and DCP between visits 0 and 1. All anti-VEGF medications reduced the number of microaneurysms (p<0.01). After treatment, changes in the FAZ in SCP and DCP corresponded with changes in visual acuity (p<0.01). Conclusion: Microaneurysms as detected by OCTA might serve as a biomarker for a clinical response to anti-VEGF treatment in the short term. The FAZ might also predict visual acuity improvement after anti-VEGF injection.