AIM: To investigate the efficacy and safety of ranibizumab (RZB group) and dexamethasone implant (DEX group) intravitreal treatments in patients with treatment-naïve center involved diabetic macular edema (DME) by means of functional and morphological assessments. METHODS: This retrospective cohort study included 50 eyes of 50 patients with DME treated either with RBZ or DEX. Best-corrected visual acuity (BCVA) and microperimetry were evaluated at baseline and during a 6-month follow-up. In addition, central macular thickness (CMT) by means of structural optical coherence tomography (OCT) and retinal capillary plexus density and choriocapillary density by means of OCT angiography were assessed in all cases. RESULTS: Functional and morphological parameters significantly improved during the study period in both groups. BCVA improved significantly in both groups with a greater increase in the DEX group compared to the RBZ group (P=0.030). Microperimetry significantly differed during follow-up between the two treatments (P=0.031). In both groups CMT significantly decreased (P<0.001) without statistically significant differences between the two groups. A statistically significant increase of deep capillary plexus density was detected in both groups at 30d after therapy. The retreatment rate was 0.70±0.10 and 0.65±0.10 in the RBZ group and 0.65±0.10 and 0.50±0.11 in DEX group at 120 and 180d respectively. Two out of 25 patients in DEX group showed intraocular pressure increase requiring hypotonic eye drops. CONCLUSION: Both treatments are very effective for DME treatment during 6mo of follow-up with a lower retreatment rate in DEX group.