Aims: This pilot study investigated the feasibility and effectiveness of the Life Skills program IPSY (Information + Psychosocial Competence = Protection) with regard to alcohol and cigarette consumption, expectations of regular use, and resistance skills in early adolescence. Thereby, we were particularly interested in the usefulness of peer educators and teachers as program facilitators in the German school setting. Methods: The design included a longitudinal assessment of a peer-led and teacher-led condition with a control group (pre- and post-assessment with a 2-year follow up; classroom-wise randomization, N = 105, T1 10 yrs. old). Results: Results of a series of ANOVAs with repeated measurement indicated that although IPSY facilitated by older peers was highly accepted by the recipients, it was ineffective regarding expectations to regular smoking, and resistance skills towards the offer of cigarettes, and it revealed negative effects on some of the students’ outcomes (in particular regarding alcohol use). In contrast, the same program facilitated by teachers had positive effects on substance use and resistance skills. Conclusions: The discussion focuses on peers’ characteristics (e. g., experiences in leading a classroom, or own consumption patterns) that might have caused the unexpected findings. This implies that, for target groups in early adolescence, in order to avoid negative outcomes, peer facilitators for universal prevention programs have to be selected and trained with great care.