Background: Tibial tuberosity (TT) transfer is a common procedure to treat patellofemoral instability in patients with elevated TT–trochlear groove (TG) distances. However, the effects of TT lateralization or medialization on patellar stability, kinematics, and contact mechanics remain unclear. Hypothesis: Progressive medialization and lateralization will have increasingly adverse effects on patellofemoral joint kinematics, contact mechanics, and stability. Study Design: Controlled laboratory study. Methods: Eight fresh-frozen cadaveric knees were placed on a testing rig, with a fixed femur and tibia mobile through 90° of flexion. Individual quadriceps heads and the iliotibial band were separated and loaded with 205 N in anatomic directions using a weighted pulley system. Patellofemoral contact pressures and patellar tracking were measured at 0°, 10°, 20°, 30°, 60°, and 90° of flexion using pressure-sensitive film behind the patella and an optical tracking system. The intact knee was measured with and without a 10-N patellar lateral displacement load, and recordings were repeated after TT transfer of 5, 10, and 15 mm medially and laterally. Statistical analysis used repeated-measures analysis of variance, Bonferroni post hoc analysis, and Pearson correlations. Results: Tibial tuberosity lateralization significantly elevated lateral joint contact pressures, increased lateral patellar tracking, and reduced patellar stability (P < .048). There was a significant correlation between mean lateral contact pressure and the TT position (r = 0.810, P < .001) at 10°. Tibial tuberosity medialization reduced lateral contact pressures (P < .002) and did not elevate peak medial contact pressures (P > .11). Conclusion: Progressive TT lateralization elevated lateral contact pressures, increased lateral patellar tracking, and reduced patellar stability. Medial contact pressure and tracking did alter with progressive TT medialization, but the changes were smaller. Clinical Relevance: Lateral patellofemoral joint contact pressures increased with progressive lateralization of the TT; medialization of the TT reduced these effects, restoring patellar stability, and did not cause excessive peak pressures. These data provide a rationale for medial TT transfer surgery in patients with elevated TT-TG distances.