The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a singleinstitution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ2 or Fisher's exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P = 0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P = 0.02). Pulmonary hypertension (PHTN) was observed in ˜ 20% of children after Bu/Mel and none after CEM (P = 0.01). CEM patients had more nephrotoxicity (P = 0.001), packed red blood cell (P = 0.02) and platelet transfusions (P = 0.008), and days on maximum pain support (P = 0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.