© 2015 Elsevier Ltd. All rights reserved. Background Humeral fracture following subpectoral biceps tenodesis has been previously reported; however, there are no published biomechanical studies reporting the resulting torsional strength of the humerus. Our purpose was to determine if there is an increased risk of humerus fracture after subpectoral biceps tenodesis with an interference screw and to determine if screw size is also a factor. We hypothesized that limbs receiving the procedure would have reduced failure torque and rotation under external rotation compared to untreated controls and that the larger screw size would result in inferior mechanical properties compared to the smaller. Methods Twenty matched pairs of embalmed cadaveric humeri were subjected to subpectoral biceps tenodesis using either a 6.25 or 8.0 mm interference screw, with the untreated contralateral limb serving as a control. Each humerus was mechanically tested in torsional external rotation to failure. Findings Maximum torque and rotation to failure were reduced in the tenodesis group compared to controls; however, there was no difference between screw sizes. When both screw sizes were combined into a single group, paired t-tests also showed similar differences. Interpretation Based on our experiment, there is an increased risk for humerus spiral fracture when subjected to torsional external rotation after subpectoral biceps tenodesis with an interference screw compared to an intact humerus; however, there is not a significant difference between a 6.25 mm and 8.0 mm screw. Surgeons may elect to use alternative fixation methods in patients at high risk (e.g., overhead throwing athletes, etc.) for torsional loads and fracture.