Objective: To explore the effectiveness of teacher-led CPR training for middle school students using standardized videos under the Train-the-Trainer model and verify its non-inferiority. Methods: A total of 400 students from 10 second-grade classes at a middle school in Deyang City were selected from December 2024 to December 2025 and randomly assigned to an experimental group and a control group, with 200 students in each group. The experimental group was taught by teachers who had undergone standardized training using standardized videos, while the control group was taught by medical personnel using the same videos and courseware. The scores of emergency medical theory knowledge, the pass rate of CPR practical skills, and the ratings on the training attitude scale were compared between the two groups after training and three months after training. Results: After training, the theoretical knowledge scores and the pass rate of practical skills in the experimental group were compared with those in the control group (P > 0.05). The 95% confidence intervals of the scores between the two groups were entirely within the non-inferiority margin. During the three-month follow-up after training, the skill retention in the experimental group was comparable to that in the control group. Both groups of students had high ratings on the training attitude scale. Conclusion: Under the Train-the-Trainer model, the effectiveness of teacher-led CPR training for middle school students using standardized videos is not inferior to that of medical personnel-led training. This model can effectively alleviate the shortage of emergency training teachers in schools and is worthy of promotion and application.