First Nations (Native American) children are greatly overrepresented in the Canadian child welfare system, and disproportionality in the substantiation of maltreatment contributes to this overrepresentation. This study explores the factors driving disproportionality in the substantiation of maltreatment and, more specifically, neglect. Data from the Canadian Incidence Study of Reported Child Abuse and Neglect (2008) are used in multivariate analyses which examine the relationship between the substantiation of maltreatment/neglect and worker assessments of case, child, household, and caregiver characteristics. These case factors fully explain disproportionality in maltreatment substantiation for First Nations and non-Aboriginal children; the disproportionality reflects underlying differences in the case, child, household and caregiver characteristics identified in First Nations and non-Aboriginal investigations. However, case factors do not fully explain disproportionality in substantiation of neglect-only investigations. Further analysis indicates that the weight that workers assigned to caregiver substance abuse, housing problems, and presence of a lone caregiver when substantiating neglect also differed for First Nations and non-Aboriginal children. Discussion of these findings explores possible explanations for these differences, and links to broader discussions around definitions of neglect and the role of substantiation in child welfare decision making processes.