This study investigates the mediating role of time perspective in the relationship between self-efficacy and the tendency toward substance abuse in adolescent girls. A total of 405 adolescent high school girls in Tehran (mean age: 16; SD: 1.01) completed the Sherer general self-efficacy questionnaire, Zimbardo time perspective inventory, and the addiction potential scale. The results indicated that a low level of self-efficacy, high levels of past negative perspective, present hedonistic, and present fatalistic perspectives, low levels of past positive perspective, and futurism predicted an increase in the tendency toward substance abuse among adolescents. On the other hand, the time perspective mediated the relationship between the tendency toward substance abuse and self-efficacy. The findings showed the importance of self-efficacy instruction in primary programs designed to prevent drug abuse among adolescents. Moreover, the preventive programs should include measures to create a balanced time perspective that is, increasing futurism and past positive perspectives, and reducing present hedonistic, present fatalistic, and past negative perspectives.