Purpose Opening wedge high tibial osteotomy (HTO) is an accepted treatment option for medial compartment knee osteoarthritis with associated varus lower limb axis in younger, more active patients. A concern with the use of this technique is that posterior tibial slope (PTS) and tibial rotation can be altered. We hypothesized that there is a tendency to increase the PTS and internal rotation of the distal tibia during the procedure and that certain intra-operative parameters may influence the amount of change that can be expected. Methods A cadaveric model and surgical navigation system were used to evaluate the influence of certain intra-operative factors of the degree of PTS and tibial rotation change observed during medial opening HTO. Parameters evaluated included: degree of osteotomy opening, knee flexion angle, location of limb support (thigh versus foot), performance of a posteromedial release, the status of the lateral cortical hinge, and the degree of osteoarthritis present in the knee. Results Combining measurements of all specimens and parameters, a mean PTS increase of 2.7° ± 3.9° and a mean tibial internal rotation of 1.5° ± 2.9° were observed. Clinically, significant changes in tibial slope (>2°) occurred in 50.4 % of corrections, while significant changes in tibial rotation (>5°) occurred in only 11.9 % of corrections. Patients with significant osteoarthritis and concomitant flexion contracture, cases where large corrections were required, and procedures in which the lateral cortical hinge was disrupted were associated with increased PTS change. The other factors evaluated did not exert a significant influence of the degree of PTS change observed. Conclusions Surgeons should be vigilant for possible PTS change, particularly in high-risk situations as outlined above. Routine use of an intra-operative measure of PTS is recommended to avoid inadvertent slope change.