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Background: Hepatitis C (HCV) is undertreated and increasing in prevalence. Its influence on outcomes following total knee arthroplasty (TKA) remains unclear. The purpose of this study is to examine the impact of HCV and prearthroplasty antiviral treatment on postoperative complications following TKA., Methods: A retrospective matched cohort study was conducted using an administrative claims database to compare postoperative complication rates following TKA for (1) patients with vs without HCV and (2) among patients with HCV, patients with antiviral treatment before TKA vs no treatment. In total, 6971 patients with HCV were matched 1:4 with 27,884 controls without HCV, and 708 HCV patients with antiviral treatment before TKA were matched 1:2 with 1416 HCV patients without treatment. Rates of joint complications at 1 and 2 years postoperatively were compared via multivariable logistic regression., Results: The HCV cohort exhibited significantly higher risk of prosthetic joint infection (PJI) than controls at both 1 (4.1 vs 2.1%; odds ratio [OR] 1.58) and 2 years (5.0% vs 2.7%; OR 1.55) postoperatively. Rates of revision TKA were also significantly higher for HCV patients at 1 (2.8% vs 1.8%; OR 1.40) and 2 years (4.1% vs 2.9%; OR 1.30). HCV patients with prearthroplasty antiviral treatment exhibited significantly lower risk of PJI at 1 (2.1% vs 4.1%; OR 0.50) and 2 years (2.7% vs 5.1%, OR 0.51) compared to patients without treatment., Conclusion: Patients with HCV have significantly increased risk of PJI and revision arthroplasty following TKA. Antiviral treatment before TKA significantly decreases the risk of PJI postoperatively., Level of Evidence: Level III., (Copyright © 2021. Published by Elsevier Inc.)