The Decomposed Theory of Planned Behavior (DTPB) was applied to develop an education program with 3D Virtual Reality (VR) animation and test its effectiveness on senior high school students with Ketamine use. The participants were 32 students with Ketamine positive urine screening from five senior high schools in Northern Taiwan. After the implementation of the 3D VR Intervention, structured questionnaire survey was then conducted. The data was analyzed by the method of path analysis. The results showed that an education program of 3D VR animation on senior high school students with Ketamine use is effective (p＜0.001). Counselor’s infl uence and resource facilitation condition were signifi cantly associated with subjective norms and perceived behavioral control, respectively. In addition, subjective norms and perceived behavioral control were significantly associated with behavior intention. The study supported the intervention effectiveness of 3D VR animation on senior high school students with Ketamine use. Students felt satisfaction after watching the innovative 3D VR animation and recognized the teaching strategy of utilizing creative media. However, they would like to watch the animations applying immersion VR instead of desktop VR. The further study is needed to explore the intervention effectiveness on stop-use behavior. Interventions should target adolescent Ketamine users, and address the critical messages on 3D VR, especially for the specifi c situations, physical and mental response and responsive life skills.