AIM: To investigate the efficacy and safety of repeated dexamethasone implants with real-life data in eyes with naive retinal vein occlusion (RVO) with macular edema (ME) at a minimum of 60mo follow-up. METHODS: In this retrospective cohort study, the data about best corrected visual acuity (BCVA), central macular thickness (CMT), serous macular detachment (SMD), hard exudate, hyperreflective foci (HRF), cystoid degeneration, pearl necklace sign, epiretinal membrane (ERM), disorganization of retinal inner layers (DRIL), ellipsoid zone and external limiting membrane (EZ-ELM) integrity, intraocular pressure (IOP) and lens condition were recorded. RESULTS: Thirty-eight eyes of 38 patients were included in the study. Thirteen patients presented with central RVO (CRVO) and 25 with branch RVO (BRVO). The mean follow-up time was 69.9±15.8mo, and the mean number of injections was 7.9±4.0. The mean BCVA gain was 25.0±36 letters, and this difference was statistically significant (P=0.021). The BCVA gain was 19.4±20.4 letters in the CRVO group, and 26.5±38.6 letters in the BRVO group (P=0.763). Besides, 21 (55.2%) of the patients achieved ≥15 letters improvement. At the end of the follow-up period, SMD was not observed in any of the patients (P=0.016). Hard exudate, HRF number were decreased; while DRIL, ERM and EZ-ELM defects were increased but not significantly. CONCLUSION: Intravitreal dexamethasone monotherapy is an effective and safe treatment option for the treatment-naive RVO-ME patients in the long-term follow-up.