IntroductionMalalignment and resulting complications are major challenges in total knee arthroplasty (TKA) which patient-specific instrumentation (PSI) is proposed to alleviate. Previous PSI meta-analyses of TKA outcomes typically do not differentiate between PSI systems and assess relatively few outcomes, so the value of their findings is limited. VISIONAIRE™cutting guides (Smith + Nephew Inc., Memphis, TN, USA) is a PSI system based on preoperative magnetic resonance and X-ray imaging. A systematic literature review (SLR) and meta-analysis, focussed specifically on VISIONAIRE, were conducted to assess TKA accuracy, intraoperative outcomes, and postoperative outcomes, compared with conventional instrumentation (CI).Materials and methodsThe SLR was performed using PubMed, Embase, and Google Scholar databases to identify relevant studies published until March 2022. Depending on statistical heterogeneity, meta-analyses were performed for outcome measures with fixed effect (I2< 50%) or random-effects models (I2≥ 50%). Dichotomous outcomes were reported as odds ratios and continuous outcomes were reported as mean differences. Descriptive analyses were performed for outcomes not amenable to meta-analysis.ResultsOutcomes for VISIONAIRE versus CI were reported in 25 studies. Compared with CI, VISIONAIRE reduced odds of mechanical outliers by 40% (p< 0.0001), with no statistically significant differences in odds of overall coronal, sagittal, or rotational plane component outliers. VISIONAIRE improved surgical efficiency (operating room, turnover, and tourniquet times reduced by 7.3% (p= 0.02), 42% (p= 0.022), and 15.9% (p= 0.01), respectively), lowering the odds of blood transfusion by 53% (p= 0.01) and shortening patients’ hospital stays (11.1% reduction;p< 0.0001). There were no significant differences between groups in incidence of postoperative complications and (descriptively analyzed) return-to-function outcomes.ConclusionOptions for PSI in TKA differ substantially, and it is important to assess the outcomes of individual systems. The current findings suggest that VISIONAIRE guides can lead to improved alignment accuracy and surgical efficiency compared with CI, without compromising postoperative safety and return-to-function outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00402-022-04698-6.