BACKGROUND: Limitation declarations are commonly deemed essential to uphold intellectual humility for scientific research, but little has been reported about the limitation statements in published original research articles. This meta-research study aims to investigate the trends of limitation statements among three leading general medical journals in the US. METHODS: This cross-sectional study will compile a data set of full-length original research articles published in the New England Journal of Medicine, Journal of the American Medical Association, and Annals of Internal Medicine between 2002 and 2022. Limitation statement will be recognized by two investigators, and a predefined set of sensitive keywords is used for sensitivity analysis. Frequency of limitation statements within the main text of research articles and trends for different study designs, including their association with the corresponding reporting guidelines, are the main measurements. We employ the Cochran-Armitage test for trend analysis. CONCLUSION: The findings of this study will provide an overview of the limitation statements in leading general medical journals in the US. The results may contribute to future research to identify factors that are associated with the presence of limitation statements.