Abstract Background/Aims Intra-articular corticosteroid injections (IACI) are recommended in the UK by NICE as an adjunctive treatment for uncontrolled pain from osteoarthritis (OA). NICE guidance states there is no evidence for therapeutic benefit lasting beyond three months, and that more evidence is needed on effectiveness at non-knee joints. We therefore aimed to assess the longer-term effect of IACI use on pain medication prescriptions among people with hand, hip, knee or shoulder OA. Methods We conducted a cohort study using UK primary care (CPRD GOLD) data for patients aged ≥20 years with a first diagnosis of OA during 2005-2019, excluding those with prior orthopaedic surgery referral or OA diagnosed at multiple joints. Exposure to IACI was defined using Read codes. The primary outcome was incident prescribing of pain medication: oral non-steroidal anti-inflammatory drugs (NSAIDs), opioids, oral corticosteroids, paracetamol, partial opioids, and topical NSAIDs. In main analyses, an instrumental variable (IV) approach was used. Index date was six months after OA diagnosis date and IV was defined as practice preference for IACI use in the year prior to index date (single and recurrent use considered separately). Outcomes were measured over five years from index date. Covariate balance was assessed, and two-step Poisson regression used where assumptions met. In secondary analyses, propensity score (PS) matching was carried out and time-varying exposure Cox models used to estimate treatment effect. Results Of 181,818 eligible patients, 92,157 (50.7%) were retained in IV analyses of single IACI and 89,103 (49.0%) of repeat IACI. Covariates were well balanced (SMD ≤0.1) across IV groups for hand (single IACI only) and knee OA, but not hip or shoulder OA. In IV analyses of hand OA, single IACI was associated with lower 5-year cumulative incidence of several pain medications including oral corticosteroids (relative risk [RR] 0.27 [95% CI 0.10, 0.76], paracetamol (RR 0.27 [0.09, 0.78] and partial opioids (RR 0.24 [0.10, 0.60]). IACI for knee OA was associated with lower 5-year cumulative incidence of most pain medications, e.g., for partial opioids a RR 0.46 [95% CI 0.34, 0.61] and RR 0.33 [0.21, 0.51] for single and recurrent IACI, respectively. Most PS matched analyses had >20,000 included patients (all joints combined), with covariates well balanced across IACI exposure status. PS matching confirmed a reduction in incidence of several pain medications associated with single IACI, e.g., lower incidence of partial opioids following IACI for any of hand, hip, knee or shoulder OA. Conclusion Our main findings suggest IACI use for hand or knee OA may reduce subsequent need for analgesics. Among knee OA patients, generally larger reductions were observed following recurrent than single IACI. In secondary analyses, single IACI for hand, hip, knee or shoulder OA was associated with lower subsequent use of partial opioids. Disclosure S. Hawley: None. A. Prats-Uribe: Grants/research support; European Medicines Agency. G. Matharu: Grants/research support; National Institute of Health and Care Research, Academy of Medical Sciences. A. Delmestri: None. D. Prieto-Alhambra: Consultancies; AstraZeneca, UCB Biopharma. Grants/research support; European Medicines Agency, Innovative Medicines Initiative, Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, UCB Biopharma. Other; Amgen, Astrellas, Janssen, Synapse Management Partners, UCB Biopharma. A. Judge: Grants/research support; National Institute of Health and Care Research, Health Data Research UK, Versus Arthritis, Healthcare Quality Improvement Partnership (HQIP), Royal College of Physicians (RCP), Tommy's, The Health Foundation. M. Whitehouse: Royalties; Taylor Francis. Member of speakers’ bureau; Heraeus. Grants/research support; National Institute of Health and Care Research, Healthcare Quality Improvement Partnership (HQIP), Ceramtec.