Aims. This study aims to evaluate the impact of metabolic syndrome in the setting of obesity on in-hospital outcomes and resource use after total joint replacement (TJR). Methods. A retrospective analysis was conducted using the National Inpatient Sample from 2006 to the third quarter of 2015. Discharges representing patients aged 40 years and older with obesity (BMI > 30 kg/m. 2. ) who underwent primary TJR were included. Patients were stratified into two groups with and without metabolic syndrome. The inverse probability of treatment weighting (IPTW) method was used to balance covariates. Results. The obese cohort with metabolic syndrome was significantly older, more likely to be female, had higher rates of Medicare insurance, and more likely to be non-Hispanic Black than the obese cohort without metabolic syndrome. In the unweighted analysis, patients with obesity and metabolic syndrome were more likely to experience cardiac, gastrointestinal, genitourinary, and postoperative anemia complications, had a longer length of stay, and were less likely to be discharged home compared to obese patients without metabolic syndrome. After adjusting for covariates using IPTW, patients with obesity and metabolic syndrome were more likely to experience postoperative anemia complications only and had lower rates of home discharge, but there were no significant differences in any other complication variables or length of stay. Conclusion. Given the variability of metabolic health in obesity, the development of tailored perioperative protocols and recommendations acknowledging this variability in metabolic health in obese patients would ultimately potentially benefit patients and improve outcomes of TJR. Cite this article: Bone Jt Open 2024;5(10):837–843