PurposeThe purpose of the present study was to compare patient-specific instrumentation (PSI) with standard instrumentation (SI) in patients undergoing total knee arthroplasty (TKA). PSI is hypothesized to have advantages with respect to component alignment; number of outliers (defined as alignment > 3° from the target alignment); operative time; perioperative blood loss; and length of hospital stay. This new surgical technique is expected to exhibit superior performance.MethodsA total of 23 randomized controlled trials (RCTs) involving 2058 knees that compared the clinical outcomes of TKA between PSI and SI were included in the present analysis; these RCTs were identified via a literature search of the PubMed, Embase, and Cochrane Library databases through March 1, 2018. The outcomes of interest included coronal, sagittal and axial component alignment (presented as the angle of deviation from the transcondylar line); number of outliers; operative time; perioperative blood loss; and length of hospital stay.ResultsThere was a significant difference in postoperative femoral axial alignment between PSI and SI patients (95% CI − 0.71 to − 0.21, p = 0.0004, I2 = 48%). PSI resulted in approximately 0.4° less deviation from the transcondylar line than SI. Based on our results, PSI reduced operative time by a mean of 7 min compared with SI (95% CI − 10.95 to − 3.75, p < 0.0001, I2 = 78%). According to the included literature, PSI reduced perioperative blood loss by approximately 90 ml compared with SI (95% CI − 146.65 to − 20.18, p = 0.01, I2 = 74%). We did not find any differences between PSI and SI with respect to any other parameters.ConclusionsPSI has advantages in axial alignment of the femoral component, operative time, and perioperative blood loss relative to SI. No significant differences were found between PSI and SI with respect to alignment of the remaining components, number of outliers, or length of hospital stay.Level of evidenceTherapeutic study (systematic review and meta-analysis), Level I.