Background: Diabetic macular edema (DME) can occur at any stage of non-proliferative and proliferative diabetic retinopathy. It is characterized by a swelling of the macular area that normally accounts for high-resolution visual acuity (VA), and DME therefore leads to visual deterioration. Objective: To compare the effect of Aflibercept (Eylea®) with Ranibizumab (Lucentis®) in treatment of diabetic macular edema by OCT. Patients and Methods: This was a prospective comparative study conducted on 32 Diabetic macular edema (DME); to compare the effect of Aflibercept (Eylea®) with Ranibizumab (Lucentis®) in treatment of diabetic macular edema by OCT. Results: Pre-operative BCVA had a highly significant positive correlation with post-operative BCVA (p < 0.0001). DM duration had a highly significant negative correlation with post-operative BCVA (p = 0.0002). Logistic regression analysis shows that; after applying (Forward method) and entering some predictor variables; the decrease in DM duration; had an independent effect on increasing the probability of patient's visual acuity improvement; with significant statistical difference (p = 0.042). By using ROC-curve analysis, Aflibercept and Ranibizumab usage showed non-significant predictive values in discrimination of improved patients from patients worsened ones (p > 0.05). Conclusion: Both aflibercept and ranibizumab improve visual acuity and decrease CMT in eyes with DME and moderate visual loss with no difference between the two drugs.