81 patients (90 knees) scheduled for total knee arthroplasty were randomized to the procedure with the use of either patient-specific instrumentation (PSI), computer navigation (NAV), or conventional instrumentation (CONV). The purpose of this study was evaluate if PSI offered significantly better results regarding alignment and clinical outcome when compared to NAV and CONV groups. Results demonstrated no significant differences between groups in overall limb alignment, coronal femoral component alignment, and coronal and sagittal tibial component alignment. The incidence of outliers in sagittal femoral component alignment was significant lower in the NAV group compared to the PSI and CONV groups. No significant differences over 2-year follow-up were noted in clinical outcomes between groups.