Purpose. To report the long‐term visual and anatomic outcomes of intravitreal injections for macular edema (ME) secondary to retinal vein occlusion (RVO) in a real‐life clinical setting. Design. Retrospective interventional case series. Methods. A total of 223 consecutive eyes with ME secondary to RVO, treated with the first three intravitreal Ranibizumab or dexamethasone injections between August 2008 and September 2018, were enrolled in the study. Subsequent retreatment was guided by best‐corrected visual acuity (BCVA) and central macular thickness (CMT) measurements, aimed at achieving macular fluid regression and BCVA stability. BCVA and CMT were recorded at baseline and at subsequent annual time points. The mean number of injections administered each year and the incidence of adverse events were recorded. Results. The mean BCVA and CMT at baseline were 0.79 logMar (SD 0.71) and 615.7 μm (SD 257.5), respectively. The mean follow‐up (FU) period was 47.8 months (min 12–max 120). At 12 months, the mean BCVA and CMT had significantly improved to 0.62 logMar (SD 0.68; p < 0.0001) and 401.04 μm (SD 183.8; p < 0.0001). Improvements remained significant at the final FU visit. Eyes with BRVO and nonischemic RVO showed significantly better visual outcomes when compared to eyes with CRVO and ischemic RVO, over the entire FU period. An average of 4.08 (SD 2.1) Ranibizumab and 1.5 (SD 0.6) Ozurdex injections were administered over the first 12 months. The number of injections decreased thereafter progressively. One eye with CRVO developed endophthalmitis and one with BRVO developed an intraocular pressure increase that was refractory to topical medications and ultimately treated with trabeculectomy. Conclusion. Intravitreal Ranibizumab and/or dexamethasone injections were found to be effective at inducing a long‐lasting improvement of BCVA and CMT in a real‐life clinical setting. A safety profile similar to that already well‐established in Ranibizumab and dexamethasone treatment was observed, as well as a steady decrease in the number of intraocular injections required. The results support intravitreal treatments for BRVO and CRVO in patient populations with similar characteristics in similar settings.