The objective of this study was to determine the effects of repeated steam sterilization cycles on the biomechanical properties of surgical screws. 42 3.5-mm and 42 2.0-mm self-tapping, cortical screws were divided into 3 groups per size and underwent autoclave sterilization for 1 (G1), 50 (G50), or 100 (G100) cycles and testing from August 2018 through June 2021. Sixty screws were then inserted into canine cadaver femurs, and biomechanical properties were measured, including peak insertional torque, torque to failure, and pullout strength, each normalized to cortical thickness. Scanning electron micrographs were taken from 24 screws, and images were blindly analyzed by 5 trained examiners. The mean normalized insertion torque for 3.5-mm screws was significantly different between G1 and both G50 and G100. The mean normalized torque to failure for 3.5-mm screws was significantly different between G1 and both G50 and G100. Axial pullout testing was found to be significantly different for 2.0-mm screws between G1 and G100. Scanning electron micrographs surface scoring identified a significant difference in 3.5-mm screws at the screw tip. The results indicate that biomechanical changes occur with repeated steam sterilizations. Specifically, peak insertional torque and torque to failure are decreased with increased sterilizations for 3.5-mm screws, whereas 2.0-mm screws were altered in pullout testing after 100 sterilizations. It is suspected that numerous sterilizations negatively alter the physical-mechanical properties of certain screw sizes. The biomechanical properties of the bone-implant interface could negatively be affected by multiple steam sterilizations during clinical setting.