BACKGROUND Intramedullary nailing has become the gold standard in the treatment of femoral shaft fractures. This procedure involves the placement of distal interlocking bolts using the freehand technique. Accurate placement of distal interlocks can be a challenging task, especially in inexperienced hands. Misplacement of distal interlocking bolts can lead to iatrogenic fracture, instability of the bone-implant construct, or even malalignment of the extremity. Repeated drilling attempts increase radiation exposure and can cause additional bony and soft tissue trauma. We hypothesize that robot-guided placement of distal interlocks is more accurate, precise, and efficient than the freehand technique. METHODS A custom-designed drill guide was mounted onto the arm of an industrial robot. We developed a special device to secure a generic block (Synbone, Malans, Switzerland) into which an intramedullary nail could be inserted in a standardized way. A metric scale allowed later measurements of the drillings. Digital images were taken from each side of the block for analysis of the drilling trajectories. The fluoroscope was adjusted to obtain perfect circles of the distal interlocking holes. The number of images necessary to achieve this was recorded. The axis was recognized automatically by using the differences in contrast between the matrix of the generic bone and the implant (intramedullary nail). The drill trajectories were then computed. The robot with the mounted drill-guide automatically moved onto the calculated trajectory. The surgeon then executed the drilling. We performed 40 robot assisted drillings in generic blocks. Freehand drilling served as our control group. RESULTS Analysis of the digital images revealed a mean deviation of 0.94 mm and 2.7° off the ideal trajectory using robotic assistance. In 100% of the cases (n = 40), the distal locking hole was hit. A mean of 8.8 images was acquired. After manual drilling, 92.5% of the distal interlocks were hit. A mean deviation of 3.66 mm and 10.36° was measured. A mean of 23.4 fluoroscopic images were needed. The differences between the two methods were statistically significant. CONCLUSIONS Robot-guided drilling increases the accuracy and precision of distal interlocking while reducing irradiation. Considering economical and logistical aspects, this application should be integrated with robot-guided fracture reduction.