Background: Induction chemotherapy plays an important role in the management of patients with high-risk neuroblastoma. Predictors of response to Induction therapy itself are largely lacking. We sought to describe clinical and biological features associated with differential response to Induction. Methods: Patients from the following COG high-risk trials with at least one disease evaluation during Induction were included: A3973; ANBL02P1; ANBL0532; and ANBL12P1. Response at end-Induction was evaluated by the 1993 International Neuroblastoma Response Criteria. The primary endpoint was partial response (PR) or better. A series of univariate analyses (Fisher's exact or chi-squared tests) were performed to compare response as a function of clinical or biologic predictor variables. For each predictor variable, the Holm-Bonferroni method was used to correct for multiple testing, using an overall α=0.05. A multivariate logistic regression model using significant predictors from univariate analyses was constructed to model PR or better. Results: The analytic cohort included 1,242 patients (79.8% with PR or better; 20.8% with CR; 9.1% with PD). Baseline factors significantly associated with a PR or better included age <18 months (87.4% with PR or better vs. 78.7% if older; p=0.0103), age <5 years (82.0% vs. 70.6% if older; p<0.0001), INSS <Stage 4 (89.0% vs. 78.4% if Stage 4; p=0.0016), MYCN amplification (85.5% vs. 77.1% if non-amplified; p=0.0006), 1p loss of heterozygosity (LOH; 85.6% vs. 76.0% if no LOH; p=0.0085), no 11q LOH (84.8% vs. 70.9% if 11q LOH; p=0.0004), and high mitosis-karyorrhexis index (MKI); 84.5% vs. 77.5% if low-intermediate MKI; p=0.0098). On multivariate analysis (n=407), the absence of 11q LOH was the only factor that remained significantly associated with PR or better (odds ratio: 1.962 compared to 11q LOH; 95% confidence interval 1.104-3.487; p=0.0216). Conclusions: Clinical and biological factors are associated with differential response to Induction chemotherapy. These findings may further improve our ability to predict treatment response.