This study interviewed adolescents about their exposure to and perceptions of substance-related social media content and substance use prevention messages. Participants (analytic sample N = 30, age 14-18 years, in CA, USA, 40% male) were recruited from Instagram and Facebook for online semi-structured interviews. An interview transcript coding guide was developed based on the interview questions and emerging themes. Most (27/30) participants reported exposure to peers using substances on social media through posts made on personal accounts. All peer posts portrayed substance use in a positive light. Most participants reported exposure to formal prevention messages on social media (i.e. public service announcements) (19/30) and in schools (i.e. drug education) (21/30; 70.0%) teaching the negative consequences of substance use. Responses to the differences between peer posts and prevention messages included dismissing prevention messages (7/30), believing that their peers were more credible (4/30), desiring comprehensive substance information (3/30) and believing that the no-use message was ineffective for at-risk youth (4/30). Messages shared by peers online significantly contrasted with prevention messages (i.e. public service announcements and drug education). This difference appeared to undermine prevention message credibility. Balanced prevention messages acknowledging the spectrum of risk and reward when using different substances may reduce dissonance and increase engagement.