ABSTRACT Purpose To evaluate the efficacy and safety of intravitreal aflibercept injections for diabetic macular edema (DME) treatment in a tertiary referral center in Greece. Methods ADMIRE was a prospective, observational cohort study of patients with DME. Efficacy was assessed by change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month 36 after treatment with intravitreal aflibercept in treatment-naive patients and previously treated patients. Safety was evaluated by recording any patients-reported events. Results Participants in the study were 94 patients with DME, 70 treatment naive and 24 previously treated with ranibizumab. At month 36 of the follow-up period, the mean change in BCVA was +7.4 letters compared to baseline (p < .001). The mean change in BCVA in treatment-naive patients was +8.9 letters and differed significantly compared to previously treated patients (+5.9 letters, p = .041). In addition, patients who received a loading dose of 5 monthly injections at the initiation of treatment provided better VA outcomes (+11.4 vs. +6.1 letters, p < .001). Accordingly, the mean CST at month 36 (369.6 ± 72.8 μm) was significantly decreased compared to baseline (479.2 ± 68.3 μm, p < .001). Overall, the mean number of injections at month 36 was 13.4. Safety analysis showed that the reported ocular adverse events during the 36-month study period were mild and not sight-threatening. Conclusion Intravitreal aflibercept was found to be safe and effective for the treatment of DME in real-life in a Greek population. Treatment-naive patients and those who received a loading dose of five consecutive monthly injections at initiation of treatment exhibited better outcomes, suggesting that early and effective treatment may prevent vision loss.