Objective: To evaluate whether exercise therapy, with or without other physical therapy interventions, is superior to placebo intervention for osteoarthritis (OA). Design: Systematic review and meta-analysis. Data sources: MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO were searched from inception to February 2021. Study selection: Randomised controlled trials (RCTs) of adults with OA investigating an intervention involving exercise therapy with a placebo comparator. Data extraction and analysis: Data were extracted and checked for accuracy and completeness by pairs of reviewers. Primary outcomes were self-reported pain, function and quality of life (QoL). Comparative treatment effects were analysed by random effects model for short- and longer-term follow up. Methodological quality was evaluated using the Cochrane risk of bias tool, and the Grading of Recommendations Assessment system was used to evaluate the certainty of evidence. Results: 13 RCTs involving 1079 patients were identified and included. Meta-analysis demonstrated improved pain (10 studies (GRADE low certainty), SMD -1.1 (95%CI -1.7 to −0.4)) and function (8 studies (GRADE low certainty), SMD -0.8 (95%CI -1.5 to −0.2)) in the short-term with exercise versus placebo, but no significant difference in the longer-term (pain 3 studies; function 3 studies). Conclusion: Current evidence demonstrates that exercise therapy is superior to placebo in the short-term for pain and function in OA. The certainty of this evidence is low to very low and further research is very likely to have an important impact on our confidence in the estimate of effects.