There has been an increase in adolescent substance use that has led to the development and implementation of prevention programs. New evidence is needed in order to improve them and optimize the resources. The aim of this paper is to use a meta-analysis to analyze the effectiveness of school drug prevention programs in Spain. Twenty-one studies that evaluated drug abuse prevention programs in schools, were published between 2002 and 2013, and that met the selection criteria were identifi ed. Preventive program effectiveness was low (d= 0.16), although it was higher at the follow-up (d= 0.30). The programs were most effective in changing attitudes (d= 0.44) towards drugs. The models of health education (d= 0.48) and social learning (d= 0.20) were also very effective, especially in combination with oral, written, and audiovisual support material (d= 0.21) and the implementation of joint programs by health education professionals and faculty members (d= 0.25). Is possible to determine the need for more rigorous evaluations of interventions to establish useful programs.