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Background: The Knee valgus brace is one of the accepted conservative interventions for patients with medial compartment knee osteoarthritis to correct the knee varus and increase functional activity level. Nevertheless, comprehensive overview of the effects of using this brace on self-reported pain activity level over time is not available. Thus, this study aimed to systematically review the effect of using this brace on pain and activity levels in the last 20 years in patients with medial compartment knee osteoarthritis.Methods: Five databases were searched to find articles from the year 2000 to the end of November 2020: Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PubMed, Web of Science, and Scopus. Two reviewers independently evaluated the available articles for eligibility and assessed quality. The risk of bias in each study was assessed by two reviewers independently according to the Strengthening the Reporting of Observational Studies in Epidemiology tool (STROBE) for the non-randomized controlled studies and the Cochrane risk-of-bias tool for the randomized controlled studies.Results: Seven randomized controlled studies and 17 cohort studies (in total 579 participants) were included in the systematic review. Most of these studies found using a knee valgus brace effective in reducing pain and improving activity level over different time intervals. The majority of the included studies (14 studies) evaluated the impact of the brace for a considerably short-term (less than 6 months). Thus, limited evidence is available on the long-term use of the knee valgus brace and its associated complications.Conclusion: The knee valgus brace is an effective conservative intervention to improve the quality of life and reduce pain during daily activities for some patients. However, the long term of using this brace is still not very convenient, and the patients who benefit most from using the brace should be identified with high methodological quality studies. [ABSTRACT FROM AUTHOR]