OBJECTIVE: 1) To identify potential moderators of the effect of therapeutic exercise explored in randomised controlled trials (RCTs) of knee and hip osteoarthritis (OA); 2) summarise the extent, strength and quality of evidence reported for moderators. DESIGN: Systematic review (PROSPERO CRD42019148074). Inclusion criteria: a) RCTs with sub-group analyses investigating potential moderator variables; b) participants with knee and/or hip OA; c) therapeutic exercise interventions compared to either no exercise control or alternative exercise intervention(s), and; d) measuring pain or physical function outcomes. Included RCTs' risk of bias and sub-group analysis quality were assessed. Data were extracted on sub-group analyses (methods and potential moderators), outcomes (pain and function) and sub-group findings (associated statistics of potential moderator∗intervention effects). Findings were analysed using narrative synthesis. RESULTS: 14 RCTs were included; 13 knee OA RCTs (n = 2743 participants) explored 23 potential moderators and 1 hip OA RCT (n = 203) explored 6 potential moderators. Sub-group analysis quality was mixed. Knee varus malalignment was the only moderator of therapeutic exercise compared to non-exercise control in 1 RCT (WOMAC-pain adjusted difference 12.7 in the neutral alignment sub-group and 1.8 in the malaligned sub-group, interaction term: p = 0.02). Varus thrust, knee laxity/instability, obesity and cardiac problems all moderated the effect of therapeutic exercise on pain or function compared to different comparison exercise. CONCLUSIONS: Therapeutic exercise may be effective for reducing pain in people with knee OA and neutral alignment but not for those with varus malalignment. The exercise moderator literature is limited. More robust evidence is required to inform sub-group exercise selection.