Background and Objectives: Retinoblastoma is the most common intraocular pediatric malignancy. Angiogenic factor expression such as VEGF (vascular endothelial growth factor) in retinoblastoma can be confirmatory angiogenic potential of this tumor. This study was performed to determine the role of angiogenesis in local invasion of retinoblastoma and its correlation with patients’ survival. Materials and methods: This clinicopathological analysis was performed on 60 paraffin- embedded eyes with adequate tumoral tissue, which were stained using a CD34 antibody. Microvessel count was carried out in three tumor areas with the richest vascularity (hot spots) at a high magnification (× 400). The obtained data were correlated with histopathological characteristics and 5-years survival. Statistical analysis of the data was performed using student t-test and ANOVA test (P<0.05). Results: Tumor with local invasion to choroids, optic nerve, sclera and cilliary body showed statistically significant higher mean vessel density (P=0.00, P=0.041, P= 0.008 and P= 0.002, respectively). In addition, a statistically significant correlation was detected between mean vascular density and 5-years survival (P=0.031). Conclusion: The results suggest that in retinoblastoma, mean vessel density has a significant role in local invasion of tumor growth and a significant correlation with patient survival. Therefore, in these patients an anti-angiogenic therapy and minute diagnostic and follow up programs should be considered to identify metastasis.