Disordered eating is highly prevalent during adolescence and has a detrimental effect on further development. Effective prevention programs are needed to prevent unhealthy developmental trajectories. This study evaluated the efficacy of the POPS-program (POtsdam Prevention at Schools), a universal school-based eating disorder prevention program for adolescents. In a cluster-randomized design, we compared the intervention group receiving the prevention program to a waiting control group. Outcomes included indicators of disordered eating and relevant risk factors for eating disorders (body dissatisfaction, internalization of the thin ideal, perceived media pressure, perfectionism, emotional element of exercise, social comparison, and perceived teasing). Questionnaires were administered at the start of the intervention, 3 and 12 months post intervention. At baseline, 1112 adolescents aged 10 to 16 years participated (49% girls; 51% intervention group). Intention-to-treat analyses with the complete data set and per-protocol analyses as a completer analysis were performed. The intervention group showed a more favorable course compared to the control group regarding all observed risk factors for eating disorders except for perceived teasing. Effect sizes were small but comparable to other primary prevention programs. At 1-year follow-up, a small but significant effect on disordered eating was observed. Results of the per-protocol analyses were mostly confirmed by the intention-to-treat analyses. Results were promising for both genders although girls benefited more regarding disordered eating and internalization of the thin ideal. Further studies are warranted examining successful program elements and whether gender-specific programs are needed.