Background Patient-specific CT-based instrumentation may reduce implant malpositioning and improve alignment in TKA. However, it is not known whether this innovation is an advance that benefits patients. Questions/purposes We evaluated (1) the precision of patient-specific TKA by comparing the incidence of outliers in postoperative alignment between TKAs using patientspecific instruments and TKAs using conventional instruments, and (2) the reliability of patient-specific instruments by intraoperatively investigating whether the surgery could be completed with patient-specific instruments alone.Methods In this randomized controlled trial, we compared patient-specific TKA instruments from one manufacturer (n = 50) with conventional TKA instruments (n = 50). Postoperative hip-knee-ankle angles, femoral component rotation, and coronal and sagittal alignments of each component were measured. The validity of the patient-specific instrument was examined using crosschecking procedures with conventional instruments during the surgeries. When the procedure could not be completed accurately with patient-specific instruments, the procedure was converted to TKA using conventional instruments, and the frequency of this occurrence was tallied.