To investigate the efficacy of single-dose intravitreal dexamethasone implantation in the treatment of persistent diabetic macular edema (DME) unresponsive to 3 consecutive ranibizumab injections over a period of 6 months. Forty-one patients with a previous history of treatment for DME including at least three consecutive intravitreal ranibizumab injections were enrolled in this retrospective study. Main outcome measures were change in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure from baseline to 6th month. At the baseline, the mean CMT was 572.4 ± 123.1 μm which improved to 264.2 ± 114.4, 317.7 ± 141.7, 410.6 ± 169.1, and 382.8 ± 181.5 μm at the 1st, 3rd, 5th, and 6th month, respectively (p < 0.05). The preoperative mean BCVA was 0.85 ± 0.54 logMAR units which improved to 0.76 ± 0.5 (p = 0.08), 0.69 ± 0.4 (p = 0.02), 0.74 ± 0.4 (p = 0.284), and 0.72 ± 0.3 (p = 0.489) logMAR units at the 1st, 3rd, 5th, and 6th months, respectively. Additional injections were required for 13 (31 %) eyes at 3rd month and 14 (34 %) eyes at 5th month due to recurrence of macular edema. Intravitreal dexamethasone implantation caused a significant improvement of BCVA and reduction of CMT in the patients with persistent DME that were unresponsive to 3 consecutive ranibizumab injections. However, retreatment before 6 months in the majority of the patients was needed despite the beneficial effects after the index procedure.