The purpose of this article is to set forth an innovative methodological protocol for culturally grounding interventions with high-risk youths in alternative schools. This study used mixed methods to evaluate original and adapted versions of a culturally grounded substance abuse prevention program. The qualitative and quantitative methods concurrently explore behaviors around drugs and alcohol, contextual variables for youth substance abuse and related factors, cultural perspectives regarding drug-related attitudes and behaviors, and the complex reasons behind students' substance use choices. Although questionnaires were used to note demographics, cultural and acculturative variables, drug use, drug and alcohol attitudes and expectancies, and school culture variables, focus groups capture the voices of the students and staff and trends that cannot be fully understood through questionnaires. In this study, focus groups aid in the understanding of student drug and alcohol choices, attitudes, and behaviors and help the researchers hone in on questions and necessary changes to future research procedures.