As the pedicle offers a strong point of attachment to the spine, several instrumentation systems using screws that go through the pedicle into the vertebral body have been developed to provide internal stability. All pedicle screw systems share the risk of damage to adjacent neural structures as a result of improper screw placement. A computer-assisted system allowing precise preoperative planning and real-time intraoperative interactive image localization has been implemented for spine instrumentation to optimize transpedicular spine fixation. A validation study was performed in an in vitro set-up drilling 20 pedicle pilot holes in lumbar vertebrae. An analysis in 77 histological cuts showed an ideal location in 70 with no case of injury to the pedicle cortex. We discuss initial clinical experience on cases of posterior lumbar stabilization. Interactive computer-assisted spine surgery provides an accurate and safe approach for transpedicular screw fixation and may provide a useful tool for optimization of spine surgery.