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High tibial osteotomy (HTO) is an effective surgical technique that can stop or inhibit the progression of unicompartmental knee osteoarthritis (KOA) to avoid or postpone the need for knee arthroplasty in patients. Whether opening-wedge high tibial osteotomy (OWHTO) is superior to closing-wedge high tibial osteotomy (CWHTO) in treating unicompartmental KOA remains controversial.Databases (Cochrane Library, EMBASE, and PubMed) were searched from their establishment to July 1, 2018 for randomized controlled trials comparing the application of OWHTO to CWHTO in patients with unicompartmental KOA. The methodological quality of each included study was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions guideline. Review Manager 5.3.5 software (Cochrane Collaboration, Oxford, UK) was used to synthesize the final results.The results will provide useful information about the effectiveness and safety of OWHTO in patients with unicompartmental KOA.The findings of the study will be published in a peer-reviewed journal.CRD4201811805.