To evaluate the effects of tibial plateau leveling osteotomy (TPLO) on femorotibial contact mechanics and 3-dimensional (3D) kinematics in cranial cruciate ligament (CrCL)-deficient stifles of dogs. In vitro biomechanical study. Unpaired pelvic limbs from 8 dogs, weighing 28-35 kg. Digital pressure sensors placed subjacent to the menisci were used to measure femorotibial contact force, contact area, peak and mean contact pressure, and peak pressure location with the limb under an axial load of 30% body weight and a stifle angle of 135 degrees. Three-dimensional static poses of the stifle were obtained using a Microscribe digitizing arm. Each specimen was tested under normal, CrCL-deficient, and TPLO-treated conditions. Repeated measures analysis of variance with a Tukey post hoc test (P <.05) was used for statistical comparison. Significant disturbances to all measured contact mechanical variables were evident after CrCL transection, which corresponded to marked cranial tibial subluxation and increased internal tibial rotation in the CrCL-deficient stifle. No significant differences in 3D femorotibial alignment were observed between normal and TPLO-treated stifles; however, femorotibial contact area remained significantly smaller and peak contact pressures in both medial and lateral stifle compartments were positioned more caudally on the tibial plateau, when compared with normal. Whereas TPLO eliminates craniocaudal stifle instability during simulated weight bearing, the procedure fails to concurrently restore femorotibial contact mechanics to normal. Progression of stifle osteoarthritis in dogs treated with TPLO may be partly the result of abnormal stifle contact mechanics induced by altering the orientation of the proximal tibial articulating surface.