Purpose <p>This study evaluated the short-term clinical outcomes of patients with refractory diabetic macular edema (DME) who switched to intravitreal faricimab (IVF) in a real-world setting.</p> Methods <p>The data from all patients with DME who did not respond adequately to anti-vascular endothelial growth factor (VEGF) therapy were analyzed retrospectively. The patients were divided into two groups, a switched group and a control group, according to whether they switched to faricimab. The following parameters were measured at the start of this study and at each follow-up time point: best-corrected visual acuity (BCVA), central macular thickness (CMT), and anatomical characteristics on spectral domain optical coherence tomography (SD-OCT). We compared baseline demographic information and treatment outcomes between the two groups, assessed both functional and structural metrics before and after IVF, and analyzed the variables affecting BCVA at follow-up.</p> Results <p>A total of 130 eyes from 105 patients were included. In the switched group, the mean BCVA improved from 0.75 ± 0.30 to 0.66 ± 0.24 at 4&#xa0;months, but the difference was not significant (<i>p = </i>0.09). The CMT notably decreased from 425.55 ± 72.54&#xa0;µm to 299.73 ± 40.09&#xa0;µm (<i>p &lt; </i>0.001). Exploratory analyses revealed that the baseline presence of disorganization of the retinal inner layers (DRIL) (<i>p = </i>0.003) and the disruption of the ellipsoid zone and external limiting membrane (EZ/ELM) (<i>p = </i>0.006) were significantly associated with poor post-treatment visual acuity. No serious adverse events were observed throughout the study period.</p> Conclusions <p>Faricimab use in eyes refractory to anti-VEGF treatment maintained visual stability, improved anatomical outcomes, and increased dosing intervals.</p>