Substance misuse is an important issue confronting youth involved with the child welfare system. The current study employed a secondary analysis of the Canadian Incidence Study of Reported Child Abuse and Neglect – 2003 (CIS – 2003) to explore risk and protective factors for substance, alcohol and drug/solvent abuse in youth age ten to 15 years. Specifically, the analysis compared youth substance abuse among all investigations and youth substance abuse among substantiated investigations of a national child welfare sample. Substance abuse in youth was almost equal between all investigations and substantiated investigations only, 14% and 16% respectively. Caregiver substance abuse was found to be a significant predictor of youth substance use in regression models; however, youth-related variables illustrated a stronger association with youth substance abuse. Negative peer involvement, irregular school attendance, and running away from home were found to have the greatest association with youth substance abuse for substantiated investigations. Authors suggest that the study’s implications are important for the need to target early intervention towards youth with a history of substance abuse, in order to reduce the probability of the youth becoming adults with substance abuse problems.