Distal locking is one of the most difficult steps in intramedullary nailing. Numerous methods can help the surgeon, but all are time-consuming and involve much irradiation. We have developed and tested a new method based on only two fluoroscopic shots that do not need to be taken in the axes of the holes. This avoids requiring the presence of an experienced fluoroscopy operator to accurately adjust the imaging device in front of the locking holes, and decreases the exposure to radiation of the patient and medical team. A 3-D model of the distal nail and of its locking holes was constructed from a pair of calibrated fluoroscopic views. Prior to this, the contours of the nail and locking holes projections had to be determined. A 3-D optical localizer allowed the tracking of reference frames fixed to the nail, imaging device, and drilling motor. A navigation system based on the model guided the surgeon during distal targeting. The robustness, accuracy, and duration of the technique were evaluated in laboratory. The range of acceptable orientations of the X-ray beam has also been determined. Twenty drilling tests were carried out on sawbones. The accuracy and the duration required by our system to perform the distal targeting shows potential suitability for clinical use. The drill passed through the nail locking holes for all of them. The accuracy was about 1.5 mm in translation and 1 degree in rotation. The total time spent on drilling did not exceed 15 min. The system was also assessed in vivo on three patients.