11 randomized controlled trials involving 972 patients undergoing total knee arthroplasty (TKA) were included in this systematic review and meta-analysis comparing kinematic alignment (KA) and mechanical alignment (MA). Pooled outcomes of interest included re-operation rates, component revision rates, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), Forgotten Joint Score (FJS), and patient preference. The analysis found no significant differences between alignment strategies for re-operation rates, component revisions, or patient-reported outcomes. However, patients who underwent bilateral TKA were more than twice as likely to prefer their kinematically aligned knee. These findings suggest that KA and MA provide comparable clinical outcomes, although KA may offer subjective benefits that are not captured by conventional outcome measures.