Background: A potential method in drilling of bone is ultrasonic-assisted drilling. In addition, during the drilling of bone, which is common in clinical surgeries, excessive heat generation and drilling force may lead to damages in bone tissue, and thus to failure of implants and fixation screws or delay in healing process. The aim of this study was to appraise efficiency of ultrasonic-assisted drilling in comparison to conventional drilling.Methods: In addition to investigating drilling force and temperature elevation, their effects on arising osteonecrosis and micro-cracks were explored in ultrasonic-assisted and conventional drilling through histopathologic assessment and microscopic imaging. In this regard, three drilling speeds and two drilling feed-rates were considered as drilling variables in the in-vitro experiments. Moreover, numerical modeling gave an insight into temperature distribution during drilling process in the both methods and compared three different vibration amplitudes. Results: Although temperature elevations were lower in the conventional drilling, the ultrasonic-assisted drilling had lesser drilling forces. Furthermore, the latter method had smaller osteonecrosis regions, and did not have micro-cracks in cortical bone and destructions in structure of cancellous bone.Conclusions: The ultrasonic-assisted drilling, which caused lesser damages to the bone tissue in both cortical and cancellous bone, was more comparatively advantageous.