Non-inferiority,as a crucial experimental approach,has gained popularity in domestic and overseas clinical research.However,discussions on research ethics and safeguarding participants'rights and interests are relatively inadequate compared to the emphasis placed on its scientific validity.This paper examines the rationality of non-inferiority by analyzing domestic and foreign literature,guiding principles,and practical cases.It explores conceptual challenges and ethical tensions related to secondary advantageous outcomes,particularly those involving cost-effectiveness considerations.It is imperative for researchers,institutional review boards,and regulatory authorities to clearly define appropriate guidelines for non-inferiority on the premise of ensuring the legitimate rights and interests of research participants.Promoting the high-quality development of clinical research needs ethical guidance in the light of pursuing the supreme good.