Orthopaedic research, and biomedical research in general, has made enormous strides to develop treatments for conditions long thought to be inevitable or untreatable;​ however, there is growing concern about the quality of published research. Considerable efforts have been made to improve overall research quality, integrity, and rigor, including meaningful proposals focused on transparency of reporting, appropriate use of statistics, and reporting of negative results. However, we believe that there is another key component to rigor and reproducibility that is not discussed sufficiently—analytical validation and quality control (QC). In this commentary, we discuss QC and method validation principles and practices that are systematically applied in the clinical laboratory setting to verify and monitor the analytical performance of quantitative assays, and the utility of applying similar practices to biochemical assays in the orthopaedic research setting. This commentary includes (1) recommendations for validation and QC practices, including examples of assay performance limitations uncovered by validation experiments performed in our laboratory, and (2) a description of an ongoing QC program developed to monitor the ongoing performance of commonly used assays in our lab. We hope that this commentary and the examples presented here will be thought-provoking and inspire further discussion and adaptation of analytical validation and QC procedures to advance our shared pursuit of high-quality, rigorous, and reproducible orthopaedic research.