Background: Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, to date, no disease modifying drug exists for this disease. In vivo studies have shown that glitazones may be used as anti-arthritic drugs. (Kobayashi, 2005; Boileau, 2007). Objectives: To determine the risk of total joint replacement (TJR) with the use of glitazones. Methods: A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n=94,609) were defined as patients >18 years of age who had undergone TJR surgery between 2000 and 2012. Controls were matched by age, gender and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) associated with use of glitazones. We additionally evaluated risk of TJR in current glitazone users compared to DM patients using other antidiabetic drugs (ADs). In order to determine a dose effect relationship, we also stratified glitazone users by total number of prescriptions prior to surgery. Results: There is no difference in risk of TKR (OR=1.11 (95% CI=0.95-1.29)) or THR (OR=0.87 (95% CI=0.74-1.02)) between glitazone users and patients not using glitazones. Furthermore, there is no difference in risk of TKR (OR=1.03 (95% CI=0.88-1.22)) and THR (OR=0.90 (95% CI=0.75-1.08)) when glitazones users are compared to other AD users. Finally, we did not find a dose response effect with increasing number of prescriptions. Conclusions: This study did not find any evidence for an anti-arthritic effect of glitazones