PURPOSE: The approach to managing patients with retinal vein occlusion and cystoid macular edema (CME) with good initial visual acuity better than 6/12 has not been investigated. This study aimed to evaluate functional and anatomical outcomes of intravitreal treatment and observation in patients with CME because of retinal vein occlusion, who presented with good initial visual acuity. METHODS: Multicenter retrospective cohort study. Seventy-nine eyes of 79 patients with CME secondary to retinal vein occlusion and initial visual acuity better than 6/12, either treated with antivascular endothelial growth factor therapy or observed. Clinical parameters and optical coherence tomography measures were recorded. Main Outcome Measure: Proportion of patients losing ≥1 line of visual acuity at 12 months. Secondary outcomes: visual and anatomical results at 12 months and 24 months, and correlation between number of injections and visual acuity outcomes. RESULTS: Fifty-three percent of patients maintained visual acuity at month 12. Visual acuity of 6/6 to 6/7.5 was maintained in 59% and 57% at 12 months and 24 months, respectively. At 24 months, the number of antivascular endothelial growth factor injections was strongly correlated with visual acuity among patients with branch retinal vein occlusion and central retinal vein occlusion. CONCLUSION: This study marks the first exploration of patients with retinal vein occlusion and initial visual acuity better than 6/12, indicating that most patients sustained good visual acuity, and antivascular endothelial growth factor treatment maintained and improved visual acuity.