Purpose: The aim of this study was to assess the efficacy of a single intravitreal dexamethasone implant (IDI) over 6 months in eyes with chronic diabetic macular edema (DME) that were resistant to intravitreal ranibizumab (IR) treatment. Methods: This retrospective study was conducted at the Ondokuz Mayis University Hospital, Samsun, Turkey. Efficacy outcomes were considered as the change from baseline in best corrected visual acuity (BCVA) and central macular thickness (CMT). Results: Thirty eyes of 20 patients with a mean age of 61.6 ± 8.8 (45-85) years were included in the study. The mean BCVA significantly increased from 0.68 ± 0.27 to 0.56 ± 0.30 logMAR (p = 0.001) and 0.57 ± 0.30 logMAR (p = 0.002) at months 1 and 2, respectively. The proportion of patients who gained 3 or more lines in BCVA was 20%. The mean CMT significantly decreased from 578.93 ± 17.95 µm at baseline to 282.10 ± 21.42, 292.26 ± 19.69, 371.70 ± 21.23, and 463.60 ± 23.16 µm at months 1, 2, 3, and 4, respectively (p = 0.001). Intraocular pressure (IOP) increase occurred in 5 (16.7%) eyes. Cataract surgery was required in 3 (13%) out of 23 phakic eyes. Conclusion: IDI provides significant benefits in visual acuity gains and anatomic improvements in eyes with chronic DME that are resistant to IR treatment. Increases in IOP and cataract progression can be observed in IDI-treated patients. However, its safety profile is acceptable.