Background: Diabetic macular edema, a manifestation of diabetic retinopathy that impairs central vision, affects approximately 750,000 people in the United States and is a leading cause of vision loss. The increasing prevalence of diabetes worldwide highlights the importance of diabetic macular edema as a global health issue. Objective: The aim of this study is to compare the clinical effects and complications of intravitreal injection of Ranibizumab and aflibercept as anti-VGEFs for treatment of patients with diabetic macular edema. Patients and methods: This cross-sectional comparative study involved 40 eyes of 32 patients approved to have diabetic macular edema. All subjects had age and sex matched and they are collected from the Ophthalmology Department, Al-Agoza Police Hospital and Sayed Galal Hospital at the period of March 2017 to March 2019. Results: Comparison between both groups I and II as regard UCVA and BCVA shows a statistically non-significant difference (P>0.05). Visual acuities before and after 6 months of injection in both groups were compared and showed a statistically significant difference as regard VA change (P < 0.05) in Ranibizumab group (I) and highly statistically significant difference (P <0.01) in Aflibercept group (II). Although the effect of both groups in treatment seems to be comparable, significance of aflibercept was superior to ranibizumab as it showed more success in treatment of DME. Conclusion: Our findings suggest a possible benefit of aflibercept over ranibizumab for treating DME. This study equally suggests better efficacy of aflibercept compared to ranibizumab, in patients with worse levels of initial visual acuity.