Purpose <p>To evaluate the clinical relevance of biomechanical experiments by conducting a systematic review of orthopedic studies that compared treatments with both a biomechanical experiment and a clinical study.</p> Methods <p>A systematic search of MEDLINE/PUBMED was performed to identify orthopedic studies that included both a biomechanical experiment and a clinical study to compare treatments. The association between a difference in the outcome of the biomechanical experiment and a difference in the outcome of the clinical study was evaluated.</p> Results <p>There were 23 studies that were included. The orthopedic specialty of the studies included trauma (<i>n</i> = 17), pediatric trauma (<i>n</i> = 2), sports (<i>n</i> = 2), and hand (<i>n</i> = 1). The anatomic areas of each study included the hip/femur (<i>n</i> = 11), shoulder/humerus (<i>n</i> = 3), elbow/forearm (<i>n</i> = 2), knee/tibia (<i>n</i> = 3), ankle/foot (<i>n</i> = 2), pelvis/acetabulum (<i>n</i> = 1), and hand (<i>n</i> = 1). The biomechanical experiments involved cadavers (<i>n</i> = 14), synthetic bone (<i>n</i> = 5), finite element analysis (<i>n</i> = 3), and animals (<i>n</i> = 1). The biomechanical experiment from each study, compared to the clinical study, was more likely to report a difference in outcomes (82.6% (19/23) vs. 30.4% (7/23), <i>p</i> = 0.0008). The findings of the biomechanical experiment and the clinical study were in agreement in 43.4% (10/23) of the studies. Studies that reported a difference in the biomechanical outcome, compared to those that did not, were not more likely to report a difference in the clinical outcome (31.6% (6/19) vs. 25.0% (1/3), <i>p</i> = 1.0).</p> Conclusions <p>The outcomes of biomechanical experiments did not correlate with clinical study outcomes. Considering these findings, the utility of biomechanical experiments in orthopedics should be reexamined.</p> Level of evidence <p>Level 3.</p>