Thirty studies including 3133 patients with end-stage knee osteoarthritis were included in this systematic review and meta-analysis comparing mechanical alignment (MA) versus kinematic alignment (KA) for total knee arthroplasty (TKA). Pooled outcomes of interest included patient-reported outcome measures (PROMs), range of motion (ROM), and revision rates. The meta-analysis showed no significant differences in PROMs such as the Knee Society Score, its function subscale, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, or Oxford Knee Score, nor in revision rates. However, a slight yet statistically significant improvement in ROM was noted favoring KA. These findings suggest minimal clinical differences between the two alignments, with ROM improvements unlikely to have clinical significance.