Background: Addiction is a significant problem among many Native American groups but has rarely been examined in urban populations. In particular, little is known about the context in which urban Native Americans first use substances. This study compares cases (people with a history of addiction) to controls (people without a history of addiction) on demographics, substance use history, context of first substance use, and polysubstance use. In addition, this appears to be the first study to overcome the lack of Native American professionals by employing and training lay community members to identify criteria of substance use disorders in survey participants. Employing community members helped foster trust that enabled the revelation of sensitive and often illegal activity. As a result, the investigators were able to recruit participants who likely would not have engaged with traditional researchers. Methods: The trained Native American lay research assistants recruited community members and administered surveys. They first asked questions regarding the criteria for substance use disorders. Individuals who were determined to have met criteria for a substance use disorder in the past were classified as cases (n = 38) and those who never met such criteria were classified as controls (n = 42). They then asked demographic, substance use, and polysubstance use questions. Lastly, eight cases and eight controls were randomly selected for a second interview by a licensed drug and alcohol counselor (LDAC) who conducted a blinded assessment regarding the presence or absence of a history of a substance use disorder. Results: Both groups reported a relatively young age of first substance use (age 16 years for cases and age 15 years for controls). Alcohol was the first substance most commonly used in both groups. Controls reported first benzodiazepine use at a younger age than cases but no other significant differences were found. Both groups reported first obtaining their first drug from family, friends, or at home (rather than a party, bar, or store). Most commonly, the location of their first use of drugs occurred at a friend's home, a party, a bar, or school rather than at their own home. Cases were marginally more likely to report that their first drug use occurred with a friend rather than with a family member when compared with controls. The majority of both groups reported that their first drug use occurred with other Native Americans rather than with non-Native Americans. Polysubstance use was common in both groups (43-45%). There were no significant differences between the groups regarding polysubstance use. The LDAC arrived at the same determination as the trained research assistants on all eight cases and eight controls.