ObjectiveClinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol—the most commonly used analgesics for OA, remains unknown.DesignNetwork meta-analysis.Data sourcesPubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.Eligibility criteria for selecting studiesRandomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.ResultsA total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=−0.12, 95% credibility interval (CrI) −1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI −0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI −0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI −1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI −0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI −1.15 to 1.24; n=9 RCTs).ConclusionsExercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166