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Although research has identified effective evidence-based depression prevention interventions for diverse youth, little is known about how the intervention process unfolds with immigrant family youth. This study utilized a qualitative approach to explore cultural and clinical differences in the implementation of Interpersonal Psychotherapy–Adolescent Skills Training (IPT-AST) in two schools, one serving youth from primarily immigrant, Asian American families and the second, youth from mostly nonimmigrant, non-Hispanic White families. A total of 131 IPT–AST sessions were audio recorded, transcribed, and coded for presence and patterns of cultural and clinical constructs. Results revealed that sessions with immigrant family youth were more likely to contain discussions of interpersonal problems characterized by estrangement, goals of spending time together with important others, mentions of emotion suppression and academic achievement expectations, conversations about acculturation, differences in value orientation, and discomfort with implementing new intervention skills. Dialogue from interventionist and youth exchanges is presented to illustrate how these themes emerged and were addressed by interventionists in a culturally responsive manner. The study highlights how IPT–AST with immigrant family and Asian American youth may unfold differently compared to youth from nonimmigrant families. Implications of findings for providers are discussed.