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INTRODUCTION: The present meta-analysis compared mechanical versus kinematic alignment in total knee arthroplasty (TKA). The outcomes of interest were patient-reported outcome measures (PROMs), range of motion (ROM), and revision rate. METHODS: This study was conducted according to the 2020 PRISMA statement. In July 2024, PubMed, Web of Science, Google Scholar, and Embase were accessed without time constraints. All the clinical studies that compared mechanical versus kinematic alignment in total knee arthroplasty were accessed. RESULTS: 30 studies (3133 TKAs) were collected. The mean duration of the follow-up was 30.8 ± 38 months. No difference was found in Knee KSS-F, Knee Society Score (KSS, P = 0.2) and its function subscale (P = 0.3), visual analogue scale (VAS, P = 0.3), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, P = 0.2), Oxford Knee Score (OKS, P = 0.5). No difference was found in the rate of revision (P = 0.4). The ROM was slightly greater in the kinematic group (P < 0.0001). CONCLUSION: PROMs and revision did not show a difference between mechanical and kinematic alignment in TKA. However, a minimal difference in the ROM was evidenced, which probably does not have clinical relevance. LEVEL OF EVIDENCE: Level IV, systematic review and meta-analysis.