Real-life data on the functional and anatomical outcome of intravitreal fluocinolone acetonide (FAc) in patients with refractory diabetic macular edema (DME). Retrospective study on 44 eyes with chronic DME that received intravitreal FAc implant and were previously treated with intravitreal Dexamethasone, triamcinolone or anti-VEGF. We assessed best-corrected visual acuity (BCVA), central maximum thickness (CMT) and foveal thickness (FT) as measured by spectral-domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering). Secondary outcomes were intraocular pressure (IOP), adverse events, time to additional treatments. The FAc implant significantly reduced the CMT (baseline 541.23 ± 155.29 µm, p < .001) and FT (baseline 460.34 ± 139.28 µm, p < .001) for up to 36 months. Despite postoperative visual improvement over time, BCVA did not significantly shift from baseline (0.55 ± 0.38 logMAR, p = .568). The FAc implant effect diminished after 21.34 ± 12.74 months. IOP increased in 9% of eyes (n = 4) but was well controlled under topical (n = 1) or surgical therapy (n = 3). Even though patients' visual recovery does not benefit significantly, the FAc implant addresses the important pillars of chronic DME therapy regarding reduced injection frequency and reduced DME.