Abstract Purpose: To compare combined phacoemulsification and intravitreal Ranibizumab (RBZ) injection versus sequential Intravitreal Raibizumab injection and phacoemulsification on the progression of diabetic macular edema (DME) both clinically (through best corrected visual acuity) and by optical coherence tomography (OCT). Setting and design: This observational study was conducted in Department of Ophthalmology, Faculty of Medicine, October 6 University. Patient and methods: Patients with non-ischemic diabetic macular edema (DME); along with, clinically significant cataract were randomly divided into two groups. Both groups received three intravitreal 0.5 mg/0.05 ml RBZ injections on monthly basis. Group (I), received the first dose combined with phacoemulsification followed by the other two injections, one and two months postoperatively. Group (II), received the first dose two weeks before phacoemulsification followed by the other two injections, one and two months from the first one. Results: The baseline mean central macular thickness (CMT) was comparable in both groups (P>0.05); however, the CMT one month after the third injection was 261±36 μm for Group (II) vs 320±65 μm for Group (I), which was statistically significant (P<0.001). Both study groups were comparable regarding the baseline mean best corrected visual acuity (BCVA) (P>0.05); however, the mean BCVA at the end of follow-up was 0.32±0.23 Log MAR for Group (II) vs 0.50±0.19 Log MAR for Group (I), which was statistically significant (P<0.001). Conclusion: Intravitreal RBZ injection has a significant clinical improving effect on both CMT and BCVA in diabetic patients with diabetic macular edema (DME) undergoing phacoemulsification; although, it is preferred to inject a single intravitreal injection two weeks before phacoemulsification to reach its peak effect in counteracting the high levels of VEGF released during the surgery.