Using image-guided surgical techniques, we propose that an industrial robot can be programmed to safely, effectively, and efficiently perform a mastoidectomy.Whereas robotics is a mature field in many surgical applications, robots have yet to be clinically used in otologic surgery despite significant advantages including reliability and precision.We designed a robotic system that incorporates custom software with an industrial robot to manipulate a surgical drill through a complex milling profile. The software controls the movements of the robot based on real-time feedback from a commercially available optical tracking system. The desired path of the drill to remove the desired volume of mastoid bone was planned using computed tomographic scans of cadaveric specimens and then implemented using the robotic system. Bone-implanted fiducial markers were used to provide accurate registration between computed tomographic and physical space.A mastoid cavity was milled on 3 cadaveric specimens with a 5-mm fluted ball bit. Postmilling computed tomographic scans showed that, for the 3 specimens, 97.70%, 99.99%, and 96.05% of the target region was ablated without violation of any critical feature.To the best of our knowledge, this is the first time that a robot has been used to perform a mastoidectomy. Although significant hurdles remain to translate this technology to clinical use, we have shown that it is feasible. The prospect of reducing surgical time and enhancing patient safety by replacing human hand-eye coordination with machine precision motivates future work toward translating this technique to clinical use.