Background: Diabetic macular edema is one of the most significant causes of blindness and severe visual impairment in patients with diabetes, which can result in reduced quality of life. Three commonly used intravitreous VEGF inhibitors aflibercept, bevacizumab and ranibizumab have been shown to be beneficial and relatively safe for the treatment of diabetic macular edema, but only aflibercept and ranibizumab are approved by the Food and Drug Administration (FDA) for this indication. Aim of the Work: To compare between the effect of ranibizumab and aflibercept in patients with diabetic macular edema as a diabetic retinopathy complication that leads to visual impairment. Patients and Methods: A prospective study of 20 patients (20 eyes) was conducted in Al-Mouneer diabetic eye center with three times injection one month apart. The patients were divided into two groups, Group A was consisted of 10 patients who received ranibizumab as 0.5 mg (0.05ml of 10mg/ml solution) an intra vitreal injection. Group B was consisted of 10 patients who received aflibercept 2 mg (0.05mL of 40mg/ml solution) as an intra vitreal injection with follow up for three months. Results: A statistically significant difference over the time through BCVA and central macular thickness with ranibizumab. There was also a statistically significant difference over the time through BCVA, central macular thickness and IOP with aflibercept. Conclusion: There was more improvement in BCVA which was significant and more reduction in central macular thickness with ranibizumab than with aflibercept. Recommendations: Larger group studies to confirm our results; longer term study for the effect of ranibizumab and aflibercept injection on the central macular thickness and IOP and comparing the effect of single injection versus multiple injections. Searching for the causes of resistance or delayed response to the intravitreal injections in some patients.