Purpose: Incidence of diabetes mellitus (DM) increases rapidly in our country as well as around the world, posing a serious threat to public health. Diabetic retinopathy (DR) is the most common microvascular complication in patients with DM since microvascular damage secondary to chronic hyperglycemia starts affecting retina in the early stages of the disease. Our aim is to evaluate the real-life outcomes of intravitreal aflibercept monotherapy in treatment naive cases with diabetic macular edema (DME). Methods: This study was retrospective case–control study. Medical charts of 75 treatment naive cases with DME were re- viewed retrospectively. A total of 127 eyes that received intravitreal aflibercept monotherapy between January 2017 and December 2018 in our Retina Unit were enrolled. Demographics and the results of their initial and all follow-up ophthalmo- logic examinations as well as the number and frequency of intravitreal shots were noted for each participant. Chi-square, Mann–Whitney U, and Wilcoxon signed-rank tests were used for statistical analysis. Results: Of the total 75 patients with a mean age of 61.2±10.4 years, 38 (50.7%) were male. Mean follow-up period was 10.2±6.3 months. Mean baseline best-corrected visual acuity and central macular thickness scores were 56.8±19.9 ETDRS let- ters and 397.8±162.4 μm, whereas they were found as 67.9±16.9 ETDRS letters and 311.0±116.8 μm at the last visit (p<0.001 and p<0.001, respectively). Aflibercept monotherapy was found to provide better anatomic prognosis in eyes with serous macular detachment (p<0.001), and better anatomic as well as functional prognosis in eyes without any concomitant vitre- omacular interface disorders (p=0.037 and p=0.042, respectively). Conclusion: Intravitreal aflibercept monotherapy proves to be an effective and reliable treatment option in treatment-naive DME cases, even in those with marked optical coherence tomography biomarkers indicating poor outcomes.