Purpose. The purpose of this study was to evaluate 2-year visual outcomes in patients with diabetic macular edema (DME) treated with anti-VEGF agents in a routine clinical setting. Methods. The medical records of patients treated with ranibizumab or aflibercept due to DME at the Eye Hospital, University Medical Centre Ljubljana, Slovenia, between January 2016 and March 2019 were retrospectively reviewed. After applying inclusion and exclusion criteria, 123 patients (123 eyes) were included in the study. Results. Baseline visual acuity (VA) was 60.9 ± 15.2 letters (median 63; range 7–85). Baseline central retinal subfield thickness (CRT) was 440.7 ± 132.5 μm (median 430; range 114–1000). No significant change in VA over 2 years was found (mean change +2.1 ± 16.8 letters (median 2; range −53–52)). However, there was a significant change in VA in the subgroup with baseline VA <70 letters (mean change +5.7 ± 17.9 letters (median 5; range −52–52)). VA gains of ≥15 letters were achieved in 25 eyes (20.3%). Changes in CRT were significant over 2 years. Patients received 4.5 ± 2.1 (median 5, range 1–9) and 2.6 ± 2.3 (median 2, range 0–8) injections in the first and second years, respectively. Conclusions. The two-year visual outcomes in this retrospective analysis appear to be comparable to previously reported outcomes in routine clinical practice. Our analysis provides some information about the effectiveness of anti-VEGF treatment in routine clinical practice in Slovenia. More intensive treatment should be implemented in the management of patients in order to achieve better visual outcomes.