INTRODUCTION: Manual therapy is an often-utilized intervention for the management of knee osteoarthritis (OA). The interpretation of results presented by these trials can be affected by how well the study designs align applicability to real-world clinical settings. AIM: To examine the existing body of clinical trials investigating manual therapy for knee OA to determine where they fall on the efficacy-effectiveness spectrum. METHODS: This systematic review has been guided and informed by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Randomized controlled trials that investigated manual therapy treatments for adults with knee OA were retrieved via searches of multiple databases to identify trials published prior to April 2023. The Rating of Included Trials on the Efficacy-Effectiveness Spectrum (RITES) tool was used to objectively rate the efficacy-effectiveness nature of each trial design. The Cochrane Risk of Bias 2.0 assessment tool (RoB-2) was used to assess the risk of bias across five domains. RESULTS: Of the 36 trials, a higher percentage of trials had a greater emphasis on efficacy within all four domains: participant characteristics (75.0%), trial setting (77.8%), flexibility of intervention (58.3%), and clinical relevance of experimental and comparison intervention (47.2%). In addition, 13.9% of the trials had low risk of bias, 41.7% had high risk of bias, and 44.4% had some concerns regarding bias. CONCLUSIONS: While many trials support manual therapy as effective for the management of knee OA, a greater focus on study designs with an emphasis on effectiveness would improve the applicability and generalizability of future trials.