With an aging population the number of total joint replacements performed due to end-stage osteoarthritis is increasing. Critically, a significant proportion of patients report dissatisfaction following surgery, with around 10% of hip and 20% of knee OA patients developing chronic postoperative pain. Obesity is a well-known risk factor for the development of OA. Pre-surgical obesity has been previously associated with worse clinical outcomes following arthroplasty. Therefore, the aim of this study was to identify factors secreted by adipose tissue that might contribute to poor outcome of arthroplasty. In total, 160 OA patients who were scheduled to undergo arthroplasty were recruited. Pre-operatively, anthropometric data were recorded. Patients completed EQ-5D health status and Oxford Knee Score (OKS) questionnaires pre-operatively and at 7 month post-operatively. Peri-operatively, synovial fluids (SF) were aspirated from the joint and the concentration of 24 adipose-secreted cytokines (adipokines) quantified by Luminex assay. Comparing pre-operative and post-operative EQ-5D index, 87% (n=139) of patients had positive response outcomes and were classified as responders. The remaining 13% (n=21) of patients, who either had a negative outcome or no improvement, were classified as non-responders. Including all patients, there was a significant correlation between ΔEQ-5D scale with BMI (Spearman r=−0.29, P=0.03) and with the degree of obesity (Spearman r=−0.40, P=0.045). Analysis of pre-operative SF revealed that non-responders had significantly lower median concentrations of resistin [1642 ng/ml (943.83516) vs. 3080 ng/ml (22356561); P<0.048], compared to responders. In addition, SF visfatin median concentrations were lower in non-responders, (0 ng/ml(00) vs. 3746 ng/ml (045 947); P=0.025], compared to responders. Poor patient outcomes in OA patients following knee and hip total joint replacement surgery are associated with differences in the pre-operative SF concentration of visfatin and resistin and with greater adiposity. Further analysis of both baseline and post-operative SF adipokines profiling together with patients anthropometrics data could provide the basis for a predictive tool to guide clinicians.