Purpose: To determine the impact of different baseline clinical characteristics on the improvement in best corrected visual acuity (BCVA) in patients with diabetic macular edema (DME) who underwent the intravitreal dexamethasone implant (DEX) Ozurdex ® . Methods: This was a single center retrospective study conducted on patients with DME, either naïve or previously treated, who were treated with one or more DEX and had a followup of at least 6 months. The main outcome measure was the proportion of DEX achieving an improvement ≥15 letters in BCVA. Results:The study analyzed 192 DEX implants administered to 97 eyes (65 patients). Among the 192 DEX analyzed, 57 (29.7%) implants achieved a BCVA improvement ≥15 letters (ETDRS) from baseline, with a mean time for achieving such improvement of 89.2 (39.7) days. Eyes who received an additional DEX and those with a duration of DME < 6 months had a greater probability of achieving a BCVA improvement ≥15 letters (odds-ratio: 2.55, p = 0.0028 and odds-ratio: 1.93, p = 0.0434). The mean (standard deviation) change in BCVA from baseline was 7.5 (14.5) letters, p < 0.0001. The mean change in central macular thickness (CMT) from baseline was −128.0 (151.0) µm, p < 0.0001. The mean number of DEX implanted was 1.9 (0.8). Four (2.1%) DEX experienced an intraocular pressure increased ≥10 mm Hg; all the cases were successfully managed with topical antiglaucoma medication. Conclusion:The results of this study confirmed previous evidence suggesting that DEX is effective for improving BCVA and CMT in patients with DME.