OBJECTIVES: We conducted a cluster randomized controlled trial to test the a priori hypothesis that students attending an interventionmiddle schoolwould be less likely to report physical adolescent relationship abuse (ARA) 1 year later comparedwith students attending a control school. Secondary objectiveswere to determine if the intervention reduced substancemisuse, bullying, and fighting. METHODS: Twenty-four Texas publicmiddle schoolswerematched by the size of student enrollment, number of economically disadvantaged students, and race and ethnicity of the student body and randomly assigned to the intervention (n =12; 1237 participants) or the control (n = 12; 1531participants) group. The intervention, Fourth R, is a classroom-based curriculumdelivered by existing teachers and consists of 21 lessons on injury prevention, substance use, and growth and development. RESULTS: Participants (50% female) self-reported ethnicity as Hispanic or Latinx (35%), Black or African American (24%), Asian American (17%), White (8%), and multiethnicity or other (16%). Among those who have dated, students in the intervention schools were less likely to report perpetrating physical ARA (intervention = 14.9% versus control = 18.3%) relative to students in the control schools (adjusted odds ratio, 0.66; 95% confidence interval, 0.43-1.00; P = .05). In the overall sample, no significant differences emerged between control and intervention groups with respect to substance misuse, fighting, and bullying. CONCLUSIONS: Themiddle school version of Fourth R is effective in reducing physical ARA perpetration over at least 1 year. The intervention did not have an effect on bullying perpetration, physical fighting with peers, and substancemisuse. Long-term assessment, especially follow-up that covers the transition to high school, is needed to examine the program benefit on key outcomes.