Objectives: To review results of orbital angiography performed during intra-arterial chemotherapy (chemosurgery) for treatment of retinoblastoma to assess the association of angiographic variability in orbitovascular anatomy with tumor response and outcomes. Methods: Medical records and 64 orbital angiograms were reviewed for 56 pediatric patients with retinoblastoma undergoing chemosurgery using a combination of melphalan hydrochloride, topotecan hydrochloride, or carboplatin. The major orbital arteries and capillary blush patterns were graded, and tumor response and recurrence were compared using the log-rank and Fisher exact tests. Results: Statistically significant variables for tumor response were lacrimal artery prominence (P=.001), previous treatment (P=.003), and lacrimal blush (P=.004). The only statistically significant variable for vitreous seed response was ciliary body blush (P=.03). Statistically significant variables influencing time to recurrence and time to enucleation were choroidal blush absence (P=.01) and lacrimal artery presence (P=.03), respectively. Conclusions: The success of intra-arterial chemotherapy is dependent on delivery of drug to the target tumor within the eye via the ophthalmic artery. Because of the small volume of drug used (0.50-1.25 mL per treatment) and the selectivity of catheterization, variables affecting orbital blood flow greatly influence drug delivery and the success of chemosurgery.