140 patients scheduled for total knee arthroplasty were randomized to have the procedure completed with the use of either patient-specific instrumentation (PSI) or conventional intramedullary guides (CONV). The purpose of this study was to evaluate if patient-specific instrumentation afforded significantly better alignment of the lower limb, and individual component alignment. Postoperative alignment was assessed via CT at 6 weeks. Clinical outcome was also assessed up to 1-year follow-up. Results demonstrated no significant differences between groups in the incidences of outliers in hip-knee-ankle angle, in the coronal, sagittal, and axial alignment of the femoral component, or in the coronal alignment of the tibial component. The incidence of outliers in the sagittal alignment of the tibial component was significant higher in the PSI group compared to the CONV group. Additionally, there were no clinically important differences in Oxford Knee Scores.