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Purpose The purpose of this meta-analysis was to compare the efficacy and imaging parameters of kinematic alignment (KA) and mechanical alignment (MA) in total knee arthroplasty (TKA) and to evaluate whether patients undergoing KA-TKA benefited more than those undergoing MA-TKA. Methods Studies comparing the efficacy of KA-TKA and MA-TKA were included after searching and screening in the database, including PubMed, Embase, Web of Science and Cochrane Database Library. A total of 1420 patients were enrolled in the study, with 736 MA-TKA and 738 KA-TKA. The primary outcomes were postoperative knee function scores including KSS series, WOMAC, KOOS and OKS. Secondary outcomes included the operative time, the length of hospital stay, knee extension/flexion angle, and some imaging parameters. The risk of bias for included studies was assessed using the Cochrane Collaborative risk-of-bias assessment tool or the Newcastle-Ottawa Scale(NOS). Results Sixteen studies were included in this meta-analysis (11 randomized controlled studies and 5 cohort studies). Primary outcomes: Knee Society score (KSS, MD = 8.36, 95% Cl: 0.83–15.90) and combined KSS (MD = 15.24, 95% CI: 5.41–25.07) were higher in KA-TKA than in MA-TKA, and other functional scores were not statistically significant in KA-TKA and MA-TKA, including knee injury and osteoarthritis outcome score (KOOS), Oxford knee score (OKS), Knee Function score (KFS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes: KA-TKA resulted in smaller medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA) compared to MA-TKA. For other outcome measures, KA-TKA showed similar results compared to MA-TKA, including hip-knee-ankle (HKA) angle, extension/flexion angle, tibial component slope angle, joint line orientation angle (JLOA), the operation time, the length of hospital stay and ligament release rate. Conclusions In our analysis results, patients undergoing KA-TKA benefit as much as patients undergoing MA-TKA. KA may be a viable reference in total knee replacement.