Introduction: There are few real-life studies on the intravitreal 0.7-mg dexamethasone implant for the treatment of diabetic macular edema (DME) conducted in Latin America. We aimed to assess the effectiveness and safety of this implant in clinical practice. Methods: Twenty-seven centers from Brazil and one from Argentina provided information on patients with DME treated with Ozurdex. The efficacy outcome variables were best-corrected visual acuity (BCVA) in Snellen and central retinal thickness (CRT). Safety was assessed by the elevation in intraocular pressure (IOP), occurrence of cataracts, and adverse events. Results: A total of 329 eyes (both treated cases and naïve eyes) from 282 patients underwent treatment. The time since diagnosis of DME ranged from 1 to 156 months. The median BCVA was 0.7 logMAR/50 letters at baseline and 0.3 logMAR/70 letters after treatment (both p < 0.001). Median CRT values decreased from 425 µm at baseline to 270 µm after treatment (p < 0.001). Increases in IOP of at least 10 mm Hg were observed in 7.4% of eyes, and 4% of eyes had cataract evolution. No cases of endophthalmitis were reported. Conclusion: These real-life results suggest that the intravitreal dexamethasone implant is effective and safe for eyes with DME.