Comparative effectiveness research (CER) is well developed in international medical research. This article analyzes the basic connotations of CER from five aspects, including selection of objective, positioning of target population, comparison of intervention scheme, identification of contrast condition and analysis of therapeutic effects. The inclusiveness and advanced nature of CER were revealed by comparing with modern medical research methods, such as evidence-based medicine, patient-important outcome and randomized controlled trials. Based on the superiority of CER, the feasibility of applying CER in clinical evaluation of traditional Chinese medicine is explored. CER should be combined with the holistic concept, syndrome differentiation and individuality-concerned treatment so as to facilitate its development in research of traditional Chinese medicine in China.