120 patients with end-stage arthritis were randomized to either undergo kinematically aligned total knee arthroplasty (TKA) with patient-specific guides or mechanically aligned TKA with intramedullary instrumentation, to compare outcomes of pain, function, and range of motion after 2 years. The results indicated that clinical outcomes, proportion of pain-free patients, and flexion active range of motion all favoured patients in the kinematically alignment TKA group over patients in the mechanically aligned TKA group at the 2-year follow-up. Alignment of the knee joint and femoral component was more valgus in the kinematically aligned TKA group whereas tibial component was more varus.