Purpose: To determine the response to radionuclide targeted therapy with I-131-metaiodobenzylguanidine (131I-MIBG) as induction therapy in high-risk neuroblastoma patients. Patients and methods: The protocol dictated at least two cycles of 131I-MIBG with a fixed dose of 7.4 and 3.7 GBq, respectively, followed by surgery, if feasible, or followed by neoadjuvant chemotherapy and surgery. This was followed by consolidation with four courses of chemotherapy myeloablative chemotherapy and autologous stem-cell transplantation (ASCT). Consolidation therapy with 13-cis-retinoic acid was given for 6 months. Results: Of 44 consecutive patients, 41 were evaluable after two courses of 131I-MIBG. The objective response rate at this point was 66%. In 24 patients, 131I-MIBG was continued as pre-operative induction treatment. Seventeen patients required additional chemotherapy before surgery. After pre-operative therapy and surgery, the overall response rate was 73%. Conclusion: First line 131I-MIBG-targeted therapy is a valuable tool in the treatment of MIBG-positive high-risk neuroblastoma patients.