Purpose: To evaluate the predictors of refractory macular edema (ME) that develops despite multiple bevacizumab injections in patients with branch retinal vein occlusion (BRVO). Methods: A total of 107 patients who followed at least 2 years were assigned to 2 groups: a refractory group (n = 56) and a responsive group (n = 51). Baseline characteristics, treatment response at 3 months, and fluorescein angiographic findings at 6 months were compared. Then we tried to identify factors associated with refractory ME development. Results: Compared to the responsive group, the refractory group had older age, longer pre-treatment duration, and shorter occlusion distance from disk. At 3 months, the refractory group exhibited lower visual acuity, thicker central retinal thickness (CRT), and larger proportion of external limiting membrane (ELM) and outer plexiform layer disruption. After 6 months, proportion of unresolved vein occlusion, macular ischemia, number of micro-aneurysms, and non-perfusion areas were higher in the refractory group. Refractory ME was associated with pre-treatment duration >= 3 months, short occlusion distance from disk, thick CRT and ELM disruption at 3 months, and unresolved vein occlusion at 6 months. Conclusion: If BRVO-ME patients exhibit the above-mentioned characteristics, they may have refractory ME, which should inform treatment decisions.