Objective: The purpose of this study was to compare the efficacy of two different intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in two treatmentnaiveand statistically equal cohorts of diabetic macular edema patients.Methods: In this retrospective study, 81 eyes of 64 treatment-naive diabetic macular edema (DME) patients were enrolled. Patients were divided into two groups andboth groups were treated [37 eyes with intravitreal 0.5 mg ranibizumab (IVR) and 44 eyes with intravitreal 2 mg aflibercept (IVA)] with three consecutive injections atintervals of one month. All patients underwent a detailed eye examination including optic coherence tomography and best corrected visual acuity (BCVA; Snellen),biomicroscopy, fundoscopy and applanation tonometry at preoperative, 1st, 2nd and 3rd month. BCVA values were converted into logarithm of the minimum angle ofresolution (logMAR) for statistical analyses. Data were evaluated with SPSS 25.0.Results: Mean BCVA (logMAR) increased from 0.58±0.28 to 0.43±0.29, 0.39±0.25 and 0.32±0.26 (p=0.001, p<0.001, p<0.001) in the IVR group and from 0.54±0.28 to0.41±0.34, 0.43±0.39 and to 0.32±0.37 (p=0.004, p=0.023, p<0.001) in the IVA group. Mean central macular thickness (CMT) decreased from 406±82 μm to 345±65μm (1st month), 332±83 μm (2nd month) and finally to 303±60 μm (3rd month) (p<0.001) in the IVR group and from 415±88 μm to 328±79 μm, 297±54 μm and finallyto 277±54 μm (p<0.001) in the IVA group, respectively. There was no significant difference between the groups in terms of BCVA (p>0.05). In the subgroup analysis, CMTgain in patients with moderate DME (CMT ≤385 μm) was found significantly better in the IVA group compared to the IVR group (1st month: 36.9 vs. 83.6, 2nd month: 36.2vs. 106.3, 3rd month: 3nd 72.7 vs. 125.1; p<0.05).Conclusion: Both anti-VEGFs were equally effective in visual outcomes. Compared to ranibizumab, aflibercept has a rapid and superior therapeutic effect in anatomicalresults, especially in moderate DME cases.