Intramedullary nailing is the standard treatment for closed and some open unstable diaphyseal tibia fractures. Fluoroscopy, while essential for proper nail placement can subject the surgical team and patient to substantial radiation. A new targeting system for tibia nail distal interlocking was developed by Orthofix to limit fluoroscopy. This prospective clinical study compares the Orthofix targeting system versus a free-hand technique for the tibial nail distal interlocking. Fifty eight consecutive patients with sixty tibial fractures amenable for nail fixation were randomly assigned into two equal groups: Group 1: Orthofix distally based distal targeting device and Group 2: a free-hand technique. In all the cases stabilization was achieved with a reamed statically locked tibial nail. Recorded data included accuracy of screw placement, duration of surgery prior to and during distal interlocking, and the fluoroscopy time prior to and during distal interlocking. Both groups revealed comparable fracture patterns. In all fractures the technical aspects of the surgical treatment were performed without complications. There was no statistically significant difference between the groups in the mean time of surgery prior to (62.02 vs. 61.01 min, P=0.92) and during distal interlocking (17.06 vs. 19.08 min, P=0.55), or in the total surgical time (81 vs. 85 min), respectively. Neither was there a statistically significant difference in the mean fluoroscopy time prior to distal interlocking (69 vs. 81 s, p=0.22) nor in the total fluoroscopy time (84 vs. 117 s). There was however, a statistically significant difference between the Orthofix and free-hand groups with regards to the mean fluoroscopy time during distal interlocking (15 vs. 36 s, P=0.01, respectively). This study demonstrates that the distally based distal targeting device by Orthofix for tibial nailing can significantly decrease the mean fluoroscopy time necessary to complete distal interlocking versus free-hand technique.