This study calculated the frequency of occurrence of gap imbalances between medial and lateral compartments at 0° flexion and within a compartment between 0° and 90° flexion, and changes in limb and knee alignment from native after computer simulation of total knee arthroplasty (TKA) with the knee set in 5° or 7° valgus at 0° flexion. TKA was simulated on 49 3D bone models of native limbs. At 0° flexion, the femoral component was set in 5° or 7° valgus from the anatomic axis of the femur, and the tibial component was set 0° to the tibial anatomic axis. At 90° flexion, internal-external rotation of the femoral component was set perpendicular to the anteroposterior axis of the trochlear groove (Method 1), parallel to the transepicondylar axis (Method 2), 3° externally rotated to the posterior condylar axis (Method 3), and gap-balanced to the tibial resection at 0° flexion (Method 4). For 5° and 7° valgus knees, the frequency of occurrence of TKAs (1) with ≥2 mm gap imbalance between compartments at 0° flexion was ≥49%, (2) with ≥2 mm gap imbalance within a compartment between 0° and 90° flexion ranged from 43-69% for Methods 1, 2, and 3, and (3) with ≥2° change in limb and knee alignment from native was ≥47%. Achieving balanced gaps between compartments at 0° flexion may often require soft tissue release. Unbalanced gaps within a compartment between 0° and 90° flexion represent a potential instability which is difficult to surgically correct. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2031-2039, 2017.