Purpose: The present study determined the efficacy and toxicity of second-course intra-arterial chemotherapy (IAC) in advanced retinoblastoma (RB) recurrence in children following failed initial IAC.Materials and Methods: A total of 24 child patients with unilateral or bilateral intra-ocular advanced RB (IIRC Group D and Group E) undergoing second-course IAC treatment after initial intra-arterial chemotherapy between September 2011 and No vember 2016 were enrolled.Global salvage,ocular adverse events,and systemic adverse events were assessed.Results: Following second-course IAC,15 (62.5％) showed complete control at 34 months follow-up,while 8 cases (33.3％) failed the treatment and 1 patient with metastatic disease (4.2％) eventually died of brain metastasis after refusing treatment.Ocular adverse events included eyelid edema (n=12),ptosis (n=5),forehead erythema (n-5),enophthalmos (n=3),and cataract (n=2).None of the patients had systemic adverse events,such as stroke or sepsis.Also,no secondary neoplasms and technical complications were observed.Conclusion: Second-course IAC is a potential alteative to enucleation in children with advanced RB,who fail an initial course of IAC.However,patients with advanced RB should be managed at experienced centers in order to consider all the alteatives before enucleation.