Our study aimed to compare the effect of self-instruction with manikin feedback to that of instructor-led method on cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) skill performance. In our randomized non-inferiority trial, 64 non-healthcare providers were randomly allocated into self-instruction and instructor-led groups. Both groups watched a 27-min standardized teaching video. Participants in the self-instruction group then performed hands-on practice on the Resusci Anne QCPR with a device-driven feedback, while those in the instructor-led group practiced manikins; feedback was provided and student's questions were answered by instructors. Outcomes were measured by blinded evaluators and SkillReporter software. The primary outcome was the pass rate. Secondary outcomes were scores of the knowledge test and items of individual skill performance. The baseline characteristics of the two groups were similar. The pass rates were 93.8% in both group (absolute difference 0%, p = 0.049 for noninferiority). The knowledge test scores were not significantly different. However, the self-instruction group performed better in some chest compression and ventilation skills, but performed worse in confirming environmental safety and checking normal breathing. There was no difference in AED skills between the two groups. Our results showed the self-instruction method is not inferior to the instructor-led method.