Background: Drug use has been noted among students in Taiwan during the past decade and schools have a role in preventing or delaying students' drug use. We developed and evaluated a school-based, drug-use prevention program integrating the theory of planned behavior (TPB) and life skills for junior high school students. Methods: We recruited 441 seventh graders from randomly selected schools: N = 143 experimental groups, N = 142 conventional groups, and N = 156 control groups. The experimental group received ten 45-minute sessions of theory-based interventions. The conventional group got traditional didactic teaching and drug refusal skills. The control group received no intervention. Results: Compared to the control group, experimental group students showed greater improvement in attitude, subjective norm, perceived behavioral control, life skills, and intention not to use drugs. Compared to the conventional group, the experimental group had significantly higher posttest scores for 4 of the 5 outcomes, including life skills (96.53 vs. 90.92, p less than 0.001), attitude (27.43 vs. 24.40, p = 0.012), subjective norm (29.51 vs. 28.06, p = 0.002), and perceived behavioral control (18.59 vs. 16.81, p less than 0.001). The conventional group scored significantly higher in behavioral intention than did the control group. Conclusion: Study results demonstrated the effectiveness of a drug-use prevention program integrating the TPB and life skills. (Contains 5 tables.)