This study was carried out to identify transdiagnostic and diagnosis-related role of Big Five personality factors in predicting adolescents’ risky behaviors. This research had a causal-comparative design and its population comprised senior secondary school students in Isfahan. For the purpose of sampling, multi-stage cluster sampling method was utilized and 1200 high school students were selected. Then, four groups of students with risky behaviors of violence, smoking, alcohol consumption and relationship with the opposite sex were identified based on their scores on Iranian Adolescents’ Risk-Taking Scale. In the next step, a semi-structured interview was conducted and NEO-FFI Inventory was also given to the subjects. To identify the patterns of transdiagnostic and diagnosis-related model, multivariate analysis of variance and discriminant analysis were utilized. The results showed that conscientiousness functioned as a transdiagnostic factor in the four groups with risky behaviors. Furthermore, neuroticism, extraversion, openness to experience, and agreeableness were diagnosis-related factors. The results of discriminant analysis showed that the participants were properly classified into the four groups. Some components, such as conscientiousness were transdiagnostic and can play a significant role in the onset and maintenance of risky behaviors. Hence, the aforementioned constructs could be used in the design of educational and therapeutic interventions since they may contribute to comorbidity through shared (transdiagnostic) processes.