21 studies evaluating the use of patient-specific instrumentation in total knee arthroplasty were included in this meta-analysis and systematic review. Pooled analyses demonstrated no significant difference between patient-specific instrumentation systems and conventional instruments in the incidence of excessive malalignment (>3 degrees deviation) in hip-knee-ankle angle. Additionally, the incidence of femoral component outliers in the coronal, sagittal, and axial planes, and tibial component outliers in the sagittal plane did not significantly differ, while tibial component outliers in the coronal plane occurred significantly more often with patient-specific instrumentation. No significant differences were found in short-term (3-month) clinical outcome measures. Two analyses which did favour patient-specific instrumentation were a lower number of surgical trays required during the procedure and shorter length of stay.