Examination of childhood risk factors for injection drug use may provide clues as to why people progress to injection drug use and it can promote identification of at-risk youth. We surveyed current injection drug users (IDUs) and individuals who never injected drugs (non-IDUs), recruited through street outreach and snowball sampling in Denver, CO. Between March 2000 and October 2003, 601 subjects (339 IDUs and 262 non-IDUs) participated in structured interviews. We examined self-reported factors in childhood that may have been influential in whether one progressed to drug injection later in life. These indicators included age at drug and alcohol initiation, childhood risk behavior, parental monitoring, family stability, and other family problems. Differences between IDUs and non-IDUs were assessed using unadjusted tests and logistic regression. Results of the data analysis indicated that IDUs were significantly younger when they first used both alcohol and marijuana, they reported higher childhood risk behavior scores, and they had less parental monitoring and less family stability as children than non-IDUs. This research may assist clinicians in defining factors that put youth at risk for problems associated with injection drug use.