Inflammatory cytokines have been proposed as potential biomarkers for damage in total knee arthroplasty (TKA). This study sought to compare the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, MCP-1, MIP-1α, MIP-3α, GM-CSF, and M-CSF) in synovial fluid of retrieved cadaveric primary TKAs, painful TKAs, and failed TKAs obtained at the time of revision. Twenty-five cadaveric specimens with primary TKAs were procured, and synovial fluid was collected. Seven synovial aspirates were collected during revision surgery from patients with failed primary TKAs, and twelve synovial aspirates were collected during clinic visits from patients with painful primary TKAs. Synovial samples were analyzed using a premixed Luminex Multiplex Screening Assay kit for detection of human inflammatory cytokines. A Kruskal-Wallis statistical test with Dunn's multiple comparison post hoc test and an assumed significance (p < 0.05) was used. Statistical analysis revealed a significant difference (p = 0.028) between IL-6 concentrations present in painful and cadaveric samples. No significant difference (p = 0.343) was found among the mean MCP-1 concentrations across the three sample groups. The cadaveric and painful samples had elevated MIP-3α compared to the revision samples upon initial inspection. Statistical analysis revealed a significant difference between cadaveric and revision sample groups. The cadaveric specimens had concentrations that were significantly elevated in comparison to the painful (p < 0.0001) and revision samples (p = 0.0015). IL-6 may be a potential biomarker for damage in a TKA. To better understand the role of MIP-3α, a future study should increase the sample size of the painful and revision groups. Future research will investigate the role of M-CSF concentrations as indicators in progression of TKA failure. Understanding the roles of these inflammatory cytokines throughout the progression of primary TKA complications may improve the diagnosis and treatment of painful TKAs.