Purpose To examine the outcome of vitrectomy for macular edema associated with branch retinal vein occlusion (BRVO) and determine the relationship between the severity of macular edema and the concentration of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in the vitreous fluid. Design Prospective observational case series. Patients and Methods Thirty-four consecutive patients (34 eyes) with macular edema associated with BRVO underwent vitrectomy. Retinal thickness was examined using optical coherence tomography. VEGF and IL-6 levels in the vitreous fluid were determined by enzyme-linked immunosorbent assay. The patients were followed for 6 months and longer after surgery. Results Visual acuity and the retinal thickness at 6 months after operation were significantly improved (P = 0.0042 and P < 0.0001, respectively). There was a significant positive correlation between the vitreous levels of VEGF and improved level of the severity of macular edema. The vitreous levels of VEGF were significantly higher in patients who showed greater improvement in the severity of macular edema (r = 0.4277, P = 0.0116). The vitreous levels of IL-6 were not significantly correlated with improvement in the severity of macular edema (r = 0.1996, P = 0.2578). Conclusion Vitrectomy appears effective for treatment of macular edema with BRVO. A higher VEGF level in the vitreous fluid may be associated with greater improvement of macular edema with BRVO.