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The role of reduction in the operative management of spondylolisthesis is controversial because of its potential complications, including neurologic deficits, prolonged operative time, and loss of reduction. The aim of this systematic review was to compare arthrodesis in situ and arthrodesis after reduction techniques with respect to clinical and radiographic outcomes and safety.We performed a comprehensive search of the PubMed, Ovid MEDLINE, Cochrane, CINAHL, Google Scholar, and Embase databases with use of the keyword “spondylolisthesis” in combination with “surgery,” “reduction,” “in situ,” “low back pain,” “high-grade,” “lumbar spine,” “lumbar instability,” and “fusion.”Eight eligible studies, containing reports of 165 procedures involving reduction followed by arthrodesis and 101 procedures involving arthrodesis in situ without reduction, were identified and included. The procedure involving reduction was associated with a significantly greater decrease in the percentage of slippage (p < 0.002) and slip angle (p < 0.003) compared with arthrodesis in situ. Pseudarthrosis was significantly more frequent in the arthrodesis in situ group compared with the reduction group (17.8% compared with 5.5%, p = 0.004). Neurologic deficits were not significantly more prevalent in the reduction group compared with the arthrodesis in situ group (7.8% compared with 8.9%, p = 0.8).On the basis on this review, the reduction of high-grade spondylolisthesis potentially improves overall spine biomechanics by correcting the local kyphotic deformity and reducing vertebral slippage. Reduction was not associated with a greater risk of developing neurologic deficits compared with arthrodesis in situ. Both procedures were associated with good clinical outcomes.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.