Patient-specific instrumentation (PSI) has recently been introduced to improve the alignment following total knee arthroplasty (TKA). However, controversy remains between PSI and conventional instrumentation. The aim of this study is to compare the accuracy of PSI with conventional instruments for total knee arthroplasty (TKA). A systematic literature search was performed in databases including PubMed, the Cochrane Library, EMBASE, and Web of Science. All of the available randomized, controlled trials (RCTs) or non-randomized, controlled trials (nRCTs) comparing PSI with conventional instruments for TKA were identified. A statistical analysis was performed of this meta-analysis. Eighteen studies with 2417 patients were included in the authors' final analysis. The results of the meta-analysis demonstrated that there were no statistical differences in outliers of the mechanical axis (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.61-1.11), the femoral component in the coronal (RR, 0.56; 95% CI, 0.32-1.05) and sagittal (RR, 0.83; 95% CI, 0.60-1.14) plane, the tibial component in the coronal (RR, 0.84; 95% CI, 0.52-1.35) and sagittal (RR, 1.04; 95% CI, 0.69-1.55) plane, and the femoral component rotation (RR, 1.02; 95% CI, 0.57, 1.83) between the 2 groups. In addition, subgroup analysis showed that the study design and imaging used for preoperative scanning did not affect the outcome of the alignment, but a different PSI system might. The authors' meta-analysis indicated that the accuracy of PSI was not superior to conventional instruments for patients undergoing TKA. Future RCTs should focus on functional outcomes and component survivorship with mid- to long-term follow-up.