High-dose chemotherapy (HDC) was investigated in high-risk neuroblastoma (HR-NBL) to reduce the risk of relapse. We report the results of the 30-year experience of a cohort of patients with HR-NBL treated with high-dose (HD) busulfan (Bu)-containing regimens. From 1980 to 2009, 215 patients aged >1 year with stage 4 NBL were treated with HD Bu-containing regimens at Gustave Roussy. These data were prospectively recorded in the Pediatric Transplantation Database. The median age at diagnosis was 40 months (12-218 months). All patients had a stage 4 neuroblastoma. NMYC amplification was displayed in 24% of the tumors. The hematopoietic support consisted of bone marrow or PBSCs in 46% and 49% of patients, respectively. The 5-year event-free survival and overall survival rates of the whole cohort were 35.1% and 40%, respectively. Age at diagnosis, bone marrow involvement and tumor response after induction chemotherapy were significant prognostic factors. Toxicity was manageable and decreased over time, owing to both PBSC administration and better supportive care. Based on this experience, HD Bu-melphalan (Mel) has been implemented in Europe and compared with Carboplatin-Etoposide-Mel in the European SIOP Neuroblastoma (SIOPEN)/HR-NBL randomized protocol. It has now become the standard HDC in the SIOPEN HR strategy.