AIM: To evaluate the safety and efficacy of a dexamethasone (DEX) intravitreal implant for diabetic macular edema (DME). METHODS: Totally 113 eyes of 84 patients were divided in three subgroups: naive patients (n=11), pseudophakic patients (n=72) and phakic patients (n=30). Inclusive criterion comprised adult diabetic patients with central fovea thickening and impaired visual acuity resulting from DME for whom previous standard treatments showed no improvement in both central macular thickness (CMT) and best corrected visual acuity (BCVA) after at least 3mo of treatment. Outcome data were obtained from patient visits at baseline and at months 1, 3, 5, 9 and 12 after the first DEX implant injection. At each of these visits, patients underwent measurement of BCVA, a complete eye examination and measurement of CMT and macular volume (MV) carried out with optical coherence tomography (OCT) images. RESULTS: Seventy-three eyes (64.5%) received a single implant, 30 (26.5%) received two implants and 10 (9%) received three implants. At baseline, average in BCVA, CMT and MV were 43.5±20.8, 462.8±145 and 12.6±2.5 respectively. These values improved significantly at 1mo (BCVA: 47.2±19.5, CMT: 339.6±120, MV: 11.11±1.4) and 3mo (BCVA: 53.2±18.1, CMT: 353.8±141, MV: 11.3±1.3) (P≤0.05). At 5mo (BCVA: 50.9±19.8, CMT: 425±150, MV: 12.27±2.3), 9mo (BCVA: 48.4±17.6, CMT: 445.5±170, MV: 12.5±2.3) and 12mo (BCVA: 47.7±18.8, CMT: 413.2±149, MV: 12.03±2.5), improvements in the three parameters were no longer statistically significant and decreased progressively but did not reach baseline values. There were no clinical differences between subgroups. Ocular complications were minimal. CONCLUSION: Patients with DEX implants show maximum efficacy at 3mo which then declined progressively, but is still better than baseline values at the end of follow-up.