Mantente REAL is a school-based universal program to prevent drug use and other problematic behaviors specifically designed to be implemented in schools at the beginning of adolescence. This program, which is a culturally adapted version of the Keepin' it REAL intervention, focuses on skills training for resisting social pressure to use drugs and improving psychosocial development. This study aims to evaluate the effectiveness of Mantente REAL on alcohol use in the Spanish context. The sample was composed of 755 adolescents from 12 state secondary schools in Spain, aged 11 to 15 (M = 12.24, SD = 0.56), 47.1% females. The 12 schools were randomly assigned to control and experimental groups, six to each condition. Pre-test and post-test questionnaires data were collected to evaluate the effectiveness of the program. The results indicated that a culturally adapted version of Mantente REAL was effective in preventing alcohol use among youth from northern and southern Spain. Students participating in the program demonstrated changes in the desired direction on alcohol frequency and intoxication episodes. Implications of these results regarding intervention programs aimed at preventing substance use in adolescence are discussed.