Background: High- risk neuroblastoma (NB; age, > 1 year; INSS stage 4) is associated with a poor outcome. At our institution, the current dose- intensive high- risk Children’ s Oncology Group protocol for advanced NB appears to have a higher surgical complication rate as compared with previous protocols. Methods: All stage 4 patients (n = 51) entered in high- risk protocols between 1995 and 2005 were analyzed. Patients in the current high- risk protocol, Children’ s Oncology Group A3973 (n = 22), were compared with those in the 2 previous protocols, CCG 3891 and POG 9341 (n = 29). Results: Patients were comparable in their mean age and tumor markers, including Shimada histology, MYCN amplification, 1p deletion, tumor origin, and extent of metastasis. However, transfusion requirement (86% vs 45% ; P = 0.0019), postoperative infection rate (32% vs 3% ; P = 0.02), and other postoperative issues including nutritional support (45% vs 3% ; P = 0.0001) were significantly higher with the current protocol. No perioperative mortality was noted in either group, and the extent of resectability and margins were similar. Importantly, with the current protocol, the survival rate was higher (P = 0.0022) and the recurrence rate was significantly lower (P = 0.0003). Conclusions: Despite higher surgical morbidity associated with the current high- risk protocol (2.59 vs 0.86 complications/person; P < 0.01), the recurrence rate is lower and interim survival rate is improved for patients with high- risk NB. Therefore, the higher surgical complication rates associated with the current high- risk protocol are acceptable. Background: High-risk neuroblastoma (NB; age,> 1 year; INSS stage 4) is associated with a poor outcome. At our institution, the current dose-intensive high- risk Children’s Oncology Group protocol for advanced NB appears to have Methods: All stage 4 patients (n = 51) entered in the high risk protocols were analyzed between 1995 and 2005. Patients in the current high risk protocol, Children’s Oncology Group A3973 (n = 22), were compared with those in the 2 previous protocols, CCG 3891 and POG 9341 (n = 29). Results: Patients were comparable in their mean age and tumor markers, including Shimada histology, MYCN amplification, However, transfusion requirement (86% vs 45%; P = 0.0019), postoperative infection rate (32% vs 3%; P = 0.02), and other postoperative issues including nutritional support 3%; P = 0.0001) were significantly higher with the curre no protocol of the current protocol, the survival rate was higher (P = 0.0022) and the recurrence rate was significantly lower (P = 0.0003 ) Conclusions: Despite higher surgical morbidity associated with the current high risk protocol (2.59 vs 0.86 complications / person; P <0.01), the recurrence rate is lower and interim survival rate is improved for patients with high- risk NB. Thus, the higher surgical complication rates associated with the current high-risk protocol are acceptable.