Background: The use of alcohol and illicit drugs during adolescence can lead to serious short- and long-term health related consequences. Despite a global trend of decreased substance use, in particular alcohol, among adolescents, evidence suggests excessive use of substances by young people in socioeconomically affluent areas. To prevent substance use-related harm, we need in-depth knowledge about the reasons for substance use in this group and how they perceive various prevention interventions. The aim of the current study was to explore motives for using or abstaining from using substances among students in affluent areas as well as their attitudes to, and suggestions for, substance use prevention. Methods: Twenty high school students (age 15-19 years) in a Swedish affluent municipality were recruited through purposive sampling to take part in semi-structured interviews. Qualitative content analysis of transcribed interviews was performed. Results: The most prominent motive for substance use appears to be a desire to feel a part of the social milieu and to have high social status within the peer group. Motives for abstaining included academic ambitions, activities requiring sobriety and parental influence. Students reported universal information-based prevention to be irrelevant and hesitation to use selective prevention interventions due to fear of being reported to authorities. Suggested universal prevention concerned reliable information from credible sources, stricter substance control measures for those providing substances, parental involvement, and social leisure activities without substance use. Suggested selective prevention included guaranteed confidentiality and non-judging encounters when seeking help. Conclusions: Future research on substance use prevention targeting students in affluent areas should take into account the social milieu and with advantage pay attention to students' suggestions on credible prevention information, stricter control measures for substance providers, parental involvement, substance-free leisure, and confidential ways to seek help with a non-judging approach from adults.