ObjectiveTo compare the clinical efficacy and complications of intra-arterial chemotherapy (IAC) and intravenous chemotherapy (IVC) for unilateral advanced retinoblastoma (RB). MethodsA retrospective clinical study. From January 2020 to January 2021, 40 patients (40 eyes) unilateral group cT2 RB patients diagnosed at Baoding Children’s Hospital and Beijing Children’s Hospital were recruited in this study. There were 22 males (22 eyes) and 18 females (18 eyes). All were monocular. All the patients were assigned to two groups according to different treatment modalities they received: IVC group and IAC group. There were 26 eyes and 14 eyes, respectively. When the tumor invades the optic nerve, choroid, sclera, anterior chamber and iris, enucleation was performed. The globe salvage rate, tumor extraocular metastasis rate, solid tumor control rate, treatment-related complications and pathological high-risk factors after enucleation were observed. The globe salvage rate and solid tumor control rate were compared between the groups by chi square test. ResultsThe globe salvage rate of IAC group and IVC group were 88.5% (23/26) and 50.0% (7/14), respectively. Solid tumor control of IAC group and IVC group were 84.6% (22/26) and 42.9% (6/14), respectively. There were statistically significant differences in globe salvage rate and solid tumor control between the two groups (χ2=7.18, 7.56; P＜0.05). Compared with IVC group, IAC group had less systemic complications, mild ocular and periocular side effects. Among 26 cases in IAC group and 14 cases in IVC group, 3 and 7 cases underwent enucleation respectively. The results of pathological examination showed that there were 2 cases and 3 cases with pathological high-risk factors in the two groups, respectively. During the follow-up period, 2 cases in IAC group had extraocular metastasis, there was no extraocular metastasis in IVC group. ConclusionCompared with IVC, IAC has the advantages of high tumor control rate, high globe salvage rate, less and mild complications, however, there is still tumor recurrence.