In recent years, peer education programs (PEPs) have put this effect to use in a positive way by providing peers that constitute positive role models for each other. Accordingly, this study was carried out to determine the effect of a PEP on the basic knowledge of adolescents about addiction and on the level of self-efficacy that is needed to avoid substance abuse. The pre-test/post-test design of this semi-experimental study used a sample of 9th year students at three high schools in Duzce, Turkey. Peer educator training (PET) with an interactively structured program was completed within a total of 20 hours. The peer educators (PEs) then implemented the program for three months to groups of 14-16 adolescents. Following program, it was determined that incidence of smoking just for once was significantly decreased and incidences of using ecstasy and non-prescription drugs just for once significantly increased. Significant increases were observed in the attitude scores of self-efficacy scale at three high schools following program. This study showed the effectiveness and applicability of the PEP in preventing substance abuse among high-school adolescents.