Abstract: Clinical practice guidelines are an important basis for clinical decision-making, but there are still many factors that prevent physicians from following the guidelines. One of the problems, the limited external validity of the guidelines, ultimately prevents the guidelines from providing an adequate basis for clinical decision-making, thus forming the gap between the guidelines and clinical decisions. Real-world research can enhance the external validity of the guidelines, provide a basis for clinical decision-making, and offer localized evidence for the guidelines, evidence of cost-effectiveness and other evidence for the guidelines. It can also monitor the implementation of the guidelines and help to make up for the lack of evidence in the formulation of traditional guidelines. Therefore, high-quality real-world studies and real-world evidence may be considered in the guideline development process to facilitate guideline optimization and serve as an aid to guideline quality improvement.