Macrophage-like cells (MLCs) are an emerging retinal biomarker. MLCs are increased in retinal vein occlusion (RVO) eyes, but their predictive value is unknown. This study investigated if MLCs can predict meaningful clinical outcomes. This prospective, cross-sectional study involved 46 eyes from 23 patients with unilateral RVO. Patients’ unaffected eyes were used as matched controls. MLCs were quantified to determine MLC density and percent image area. We collected demographic, clinical, ocular, and imaging characteristics at the time of MLC imaging. We additionally recorded best corrected visual acuity (BCVA) and number of intravitreal injections at 6 months and 12 months post-imaging. MLC density and percent area increased by 1.86 (p = 0.0266)- and 1.94 (p = 0.0415)-fold in RVO compared to control eyes. We found no significant correlation between MLC parameters and any baseline characteristic. MLC density was positively correlated with the number of intravitreal injections at 6 months (n = 12, r = 0.62, p = 0.03) and 12 months (n = 9, r = 0.80, p = 0.009) post-imaging. MLC percent area was correlated with LogMAR BCVA change over 12 months (n = 17, r = 0.57, p = 0.02). High MLC counts correlated with more future intravitreal injections and worse visual acuity outcomes, suggesting that MLCs are a biomarker for treatment resistant RVO eyes.