Purpose: To investigate the long-term effect of intravitreal dexamethasone (DEX) implant and anti-vascular endothelial growth factor (VEGF) injection on macular edema (ME) secondary to retinal vein occlusion (RVO) in a real-world setting. Methods: The medical records of RVO-ME cases, with intravitreal injections and followed-up for at least 5 years, were retrospectively reviewed. Changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were primary outcomes. Images of fluorescence angiography (FA) and swept-source optical coherence tomography angiography (OCTA) were analyzed. Foveal avascular zone (FAZ) metrics and perfusion density at the last visit were also compared between the two treatments. Results: A total of 16 patients were recruited, 8 in the anti-VEGF group and 8 in the DEX group. At the 5th year, the BCVA and the CMT in the DEX group were not different from those in the anti-VEGF group (0.69 ± 0.36 LogMAR vs 0.57 ± 0.30 LogMAR, P = 0.574; 183.25 ± 97.31 μm vs 195.38 ± 40.92 μm, P = 0.442). Compared with the anti-VEGF group, the DEX group had higher FAZ circularity index (0.57 ± 0.14 vs 0.68 ± 0.14, P = 0.130) and higher retinal perfusion density (0.45 ± 0.02 vs 0.39 ± 0.03, P = 0.001), especially in the deep capillary plexus. Conclusion: DEX implant and anti-VEGF injection had comparative long-term effects on RVO-ME. Compared with the anti-VEGF treatment, the DEX treatment had advantages in maintaining retinal perfusion in patients with RVO.