The production of polyethylene wear debris in total knee arthroplasty (TKA) is due to multiple factors. In particular, inadequate implant alignment and high bearing surface contact stresses are associated with polyethylene failure. Optimal implant placement and soft tissue balancing may contribute to reducing wear and the production of polyethylene particles. We present a case in which a quantitative technique was used to measure tibiofemoral contact stresses during implantation of a total knee prosthesis in vivo. In a knee with preoperative varus and fixed flexion deformity, medial compartment contact stresses after initial resection were reduced from 14.3 MPa to 11.3 MPa in neutral alignment by additional bone resection. Posterior cruciate release was required to reduce contact stresses further and to provide satisfactory balance between medial and lateral compartments, as determined by the operating surgeon, and was confirmed by the measurement system (3.8 MPa medially; 3.0 MPa laterally). This technique has potential to fine-tune implant positioning and ligament balancing during TKA.