Using structural equation modeling, we examined the relationship of Hispanicism on recent substance use and whether Americanism moderated the effect in a sample of 1,141 Hispanic adolescents. The Bicultural Involvement Questionnaire (BIQ) was used to determine the degree of individual comfort in both Hispanic (Hispanicism) and American (Americanism) cultures. Hispanicism was associated with greater family functioning (β = .36, p < .05) and school bonding (β = .31, p < .01); Americanism moderated the effect of Hispanicism on substance use (β = .92, p < .01). Findings suggest that Hispanic culture was protective against substance use; however, those effects differed depending on level of Americanism.