Background Exposure to media violence might have detrimental effects on psychological adjustment and is associated with aggression-related attitudes and behaviors. As a result, many media literacy programs were implemented to tackle that major public health issue. However, there is little evidence about their effectiveness. Evaluating design effectiveness, particularly regarding targeting process, would prevent adverse effects and improve the evaluation of evidence-based media literacy programs. Objectives The present research examined whether or not different relational lifestyles may explain the different effects of an antiviolence intervention program. Research design Based on relational and lifestyles theory, the authors designed a randomized controlled trial and applied an analysis of variance 2 (treatment: experimental vs. control) x 4 (lifestyle classes emerged from data using latent class analysis: communicative vs. autonomous vs. meta-reflexive vs. fractured). Subjects Seven hundred and thirty-five Italian students distributed in 47 classes participated anonymously in the research (51.3% females). Measures Participants completed a lifestyle questionnaire as well as their attitudes and behavioral intentions as the dependent measures. Results The results indicated that the program was effective in changing adolescents' attitudes toward violence. However, behavioral intentions toward consumption of violent video games were moderated by lifestyles. Those with communicative relational lifestyles showed fewer intentions to consume violent video games, while a boomerang effect was found among participants with problematic lifestyles. Conclusion Adolescents' lifestyles played an important role in influencing the effectiveness of an intervention aimed at changing behavioral intentions toward the consumption of violent video games. For that reason, audience lifestyle segmentation analysis should be considered an essential technique for designing, evaluating, and improving media literacy programs.