OBJECTIVE 131I-metaiodobenzylguanidine (131I-mIBG) has a significant targeted antitumor effect for neuroblastoma. However, currently there is a paucity of data for the use of 131I-mIBG as a "front-line" therapeutic agent in those patients with newly diagnosed high-risk neuroblastoma as part of the conditioning regimen for myeloablative chemotherapy (MAC). OBJECTIVE To evaluate the feasibility of upfront consolidation treatment with 131I-mIBG plus MAC and hematopoietic stem cell transplantation (HSCT) in high-risk neuroblastoma patients. METHODS A retrospective, single-center study was conducted from 2003-2019 on newly diagnosed high-risk neuroblastoma patients without progressive disease (PD) after the completion of induction therapy. They received 131I-mIBG infusion and MAC followed by HSCT. RESULTS A total of 24 high-risk neuroblastoma patients were enrolled with a median age of 3.0 years at diagnosis. After receiving this sequential consolidation treatment, 3 of 13 patients who were in partial response (PR) before 131I-mIBG treatment achieved either complete response (CR) (n = 1) or very good partial response (VGPR) (n = 2) after HSCT. With a median follow-up duration of 13.0 months after 131I-mIBG therapy, the 5-year event-free survival and overall survival rates estimated were 29% and 38% for the entire cohort, and 53% and 67% for the patients who were in CR/VGPR at the time of 131I-mIBG treatment. CONCLUSIONS Upfront consolidation treatment with 131I-mIBG plus MAC and HSCT is feasible and tolerable in high-risk neuroblastoma patients, however the survival benefit of this 131I-mIBG regimen is only observed in the patients who were in CR/VGPR at the time of 131I-mIBG treatment.