Background: Life skills programs are effective tools to combat youth substance use. However there is a lack of studies concerning their effectiveness in Europe. Objective: This study investigated the 1 year follow up effects and the program implementation of a life skills school-based intervention (IPSY: Information + Psychosocial Competence = Protection) aimed at preventing alcohol use, in German and Italian adolescents. Methods: Participants were 1131 German (57 % intervention group, mean age 10.45 years, 54 % females), and 159 Italian adolescents (45 % intervention group, mean age 11.14 years, 50 % females). Using a quasi-experimental design, data were gathered before the intervention (t1), after (2-7 months later, t2), and 1 year after the post-test (t3), thus covering a time span of about 1.5 years. MANOVAs and ANOVAs with repeated measurements were performed. Results: IPSY was well accepted in both the German and Italian schools. German and Italian youth who participated in the program decreased their consumption of wine. German youth who participated in the IPSY-program decreased their expected alcohol consumption and increased their knowledge of assertive behaviors, school involvement, and resistance to peer pressure, compared to the control group. Italian youth in the intervention group also increased in assertive behaviors and the perception of being appreciated by others, relative to the control group. In both countries, beer consumption, communication skills and problem solving were not affected. Conclusions: Our study suggests that life skills-based programs may be a useful tool in the prevention of risk behaviors in adolescence in a broader European context.