Total knee replacements (TKR) have historically been implanted perpendicular to the mechanical axis of the knee joint, with a commensurate external rotation of the femur in flexion relative to the posterior condylar axis (PCA). Although this mechanical alignment (MA) method has typically offered good long-term survivorship of implants, it may result in alignment of the implant that departs significantly from the native Joint Line (JL) in extension and flexion for a considerable portion of the patient population. There is a growing interest with surgeons to implant TKR components more closely aligned to the natural JL (Anatomic Alignment-AA) of the patientâs knee joint to reduce the need for soft tissue releases during surgery, potentially improving knee function and patient satisfaction. Using a previously-validated finite element model of the lower extremity, implant- and alignment-specific loading conditions were developed and applied in a wear experiment via a six-degree-of-freedom joint simulator. MA was defined as 0° Joint Line (JL), 0° varus hip-knee-ankle (HKA) angle, and 3° external femoral rotation. AA was defined as 5° varus JL, 3° varus HKA, and 0° femoral rotation. The experiment returned wear rates of 3.76â±â0.51âmg/million cycles (Mcyc) and 2.59â±â2.11âmg/Mcyc for ATTUNEÂź cruciate-retaining (CR) fixed bearing (FB) in MA and AA, respectively. For ATTUNE posterior-stabilized (PS) FB in AA, the wear rate was 0.97â±â1.11âmg/Mcyc. For ATTUNE CR rotating platform (RP), the wear rates were 0.23â±â0.19âmg/Mcyc, 0.48â±â1.02âmg/Mcyc in MA and AA respectively. Using a two-way ANOVA, it was determined that there was no significantly difference in the wear rates between AA and MA ( pâ=â0.144) nor the wear rate of ATTUNE PS FB in AA significantly different from either ATTUNE CR FB or ATTUNE CR RP.