Background Surgical techniques for proximal biceps tenodesis that include penetration of the posterior humeral cortex for fixation may pose risk to the surrounding neurovascular structures. Hypothesis The risk of neurologic injury with techniques that involve penetration of the posterior humeral cortex for fixation in proximal biceps tenodesis will increase as the tenodesis site moves proximally from the subpectoral to the suprapectoral location. Methods Proximal biceps tenodesis was performed on 10 cadaveric upper extremities with 3 separate techniques. The proximity of the hardware to the relevant neurovascular structures was measured. The distances between the tenodesis site and the relevant neurovascular structures were measured. Results The guide pin was in direct contact with the axillary nerve in 20% of the suprapectoral tenodeses. The distance between the axillary nerve and the tenodesis site was 10.5 ± 5.5 mm for the suprapectoral location, 36.7 ± 11.2 mm in the subpectoral scenario, and 24.1 ± 11.2 mm in the 30° cephalad scenario (P = .003). The distance between the radial nerve and the anterior tenodesis site was 41.3 ± 9.3 mm for the suprapectoral location and 48.0 ± 10.7 mm for the subpectoral location. The distance of the musculocutaneous nerve from the tenodesis site was 28.4 ± 9.2 mm for the suprapectoral location and 37.4 ± 11.2 mm for the subpectoral location. Conclusion In a cadaveric model of open biceps tenodesis, penetration of the posterior humeral cortex at the suprapectoral location results in proximity to the axillary nerve and should be avoided. Subpectoral bicortical button fixation drilled perpendicular to the axis of the humerus was a uniformly safe location with respect to the axillary nerve.