Macular edema secondary to retinal vein occlusion (RVO) is a sight-threatening condition. Previous studies showed that early responders (ERs) who respond well to anti-VEGF injections within 3 months of treatment have better outcomes, as measured by best visual acuity (BVA) and central subfield thickness (CST) at 12 months postinjection initiation compared with limited early responders (LERs). This study analyzed whether ER eyes continue to respond better than LER eyes over longer periods. This study also aimed to identify baseline comorbidities associated with response status. Retrospective cohort study. Patients aged > 18 years with RVO-related macular edema treated with anti-VEGF injections. Patients were categorized as ERs or LERs. Limited early responder eyes were defined as having CST reduction < 10%, BVA gain < 5 ETDRS letters, or both at 3 months after anti-VEGF initiation. Best visual acuity and CST changes over the 24- and 36-month period after the first anti-VEGF treatment were compared between ERs and LERs. Patient characteristics and systemic comorbidities were identified by chart review. Statistical analysis involved the Levene test, Welch t test, and Welch analysis of variance. Best visual acuity and CST changes over the initial 24-month and 36-month periods after treatment. The 24-month cohort included 68 ERs and 39 LERs, and the 36-month cohort included 58 ERs and 33 LERs. At the 24-month time point, there were significant differences in BVA and CST gains between ERs (+19.8 letters,-221.2 um) and LERs (-2.4 letters,-90.1 um; P < 0.001, P < 0.01). Similarly, at 36 months, there were significant differences in BVA and CST gains between ERs (+17.7 letters,-229.3 um) and LERs (+1.3letters,-128 um; P < 0.001, P < 0.05). After controlling for differences in baseline BVA and CST, only the 24-month change in BVA remained significant (P < 0.001). There were no significant associations between response status and cardiopulmonary, endocrine, and oncologic comorbidities. Early responder eyes with branched retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) have better functional responses to anti-VEGF injections at 24 months compared with LER eyes, even after controlling for baseline differences. Early identification of eyes as ERs or LERs in BRVO and CRVO may predict long-term functional prognoses. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.