Pedicle screw fixation is a technique used to provide rigid fixation in thoracolumbar spine surgery. Safe intraosseous placement of pedicle screws is necessary to provide optimal fixation as well as to avoid damage to adjacent anatomic structures. Despite the wide variety of techniques available, none thus far has been able to fully eliminate the risk of malpositioned screws. Intraoperative 3-dimensional navigation (I3DN) was developed to improve accuracy in the placement of pedicle screws. To our knowledge, no previous studies have investigated whether infection rates are higher with I3DN. A single-institution, retrospective study of patients age > 18 undergoing thoracolumbar fusion and instrumentation was carried out and use of I3DN was recorded. The I3DN group had a significantly greater rate of return to the operating room for culture-positive incision and drainage (17 (4.1%) vs. 1 (0.6%), p = 0.025). In multivariate analysis, the use of I3DM did not reach significance with an OR of 6.49 (0.84–50.02, p = 0.073). Post-operative infections are multifactorial and potential infection risks associated with I3DN need to be weighed against the safety benefits of improved accuracy of pedicle screw positioning.