The insertion site for an antegrade femoral intramedullary nail in the treatment of a femoral shaft fracture has traditionally been performed using a free-hand technique. An inappropriate starting point can result in suboptimal nail insertion leading to malreduction, or iatrogenic fracture. Furthermore, repeated attempts to establish the optimal starting point can cause additional soft tissue trauma and radiation exposure. In the following study we compared a robot-guided technique with the standard free-hand technique for establishing the entry point of an antegrade femoral nail. We hypothesized that the robot-guided technique is more reliable and efficient.A custom-made drill-guide was mounted onto the arm of an industrial robot. Two orthogonal fluoroscopic images were acquired from the proximal femur of five cadaveric human specimens. Images were processed with a special software in order to create an enhanced contour-recognition map from which the bone axes were automatically calculated. The drilling trajectory was computed along the extension of the bone-axis. The robot then moved the drill-guide on this trajectory toward the entry point. The drilling was then performed by the surgeon. In the control group, five cadaveric human femora were utilized to manually establish the starting point using the free-hand technique.100% of the intramedullary cavities were successfully accessed with both the robot-guided and the manual techniques. In the manual technique repositioning of the drill was necessary in three out of five cases. The mean number of acquired fluoroscopic images was significantly reduced from 11.6 (manual) to 4 (robot-guided).Robot-assisted drilling of the entry-point in antegrade femoral nailing is more reliable and requires fewer radiographic images than the free hand technique. Yet, based on economical and logistical considerations, its application will probably only be accepted when a concomitant application for fracture reduction is available.