The purpose of this quasi-experimental study was to evaluate a large-scale implementation of the Olweus Bullying Prevention Program with children and youth in grades 3–11 in the U.S. Two major sets of analyses are presented, one following 210 schools over two years (Study 1; n = 70,998 at baseline) and the other following a subsample of 95 schools over three years (Study 2; n = 31,675 at baseline). Schools were located in 49 counties in central and western Pennsylvania. The Mplus 7.0 program was used to analyze the data which had a multilevel structure, with students nested in schools and program effects based on school-aggregated outcome variables. For almost all grades, there were clear reductions in the two key dimensions, being bullied and bullying other students. Average Absolute Change amounted to approximately 3%, implying that almost 2000 students had escaped being bullied in the two-year study. School-level Cohen's d's were large or fairly large. The longitudinal analyses documented increases in students' expressions of empathy with bullied peers, marked decreases in their willingness to join in bullying, and perceptions that their primary teacher had increased his or her efforts to address bullying. Overall, effects were stronger the longer the program had been in place. The analyses provided strong support for the effectiveness of the OBPP with U.S. students in elementary, middle, and early high school grades in Pennsylvania schools. Future research is warranted to assess program effectiveness in different racial/ethnic and community settings and to examine the relation between fidelity of implementation and outcomes.