BackgroundTo reduce the substantial clinical and financial burden of periprosthetic joint infection (PJI), some surgeons advocate for the use of antibiotic-loaded bone cement (ALBC) in primary total knee arthroplasty (TKA), although its effectiveness continues to be debated in the literature. The purpose of this study was to determine whether the routine use of ALBC is cost-effective in reducing PJI after primary TKA. MethodsWe retrospectively reviewed a consecutive series of patients undergoing cemented primary TKA at two hospitals within our institution from 2015 to 2017. We compared demographics, comorbidities, costs, and PJI rates between patients receiving ALBC and plain cement. We performed a multivariate regression analysis to determine the independent effect of ALBC on PJI rate. We calculated readmission costs for PJI and reduction in PJI needed to justify the added cost of ALBC. ResultsOf 2511 patients, 1077 underwent TKA with ALBC (43%), with no difference in PJI rates (0.56% vs 0.14%, P = .0662) or complications (1.2% vs 1.6%, P = .3968) but higher cement costs ($416 vs $117, P < .0001) and overall procedure costs ($6445 vs $5.968, P < .0001). ALBC had no effect on infection rate (P = .0894). Patients readmitted with PJI had higher overall 90-day episode-of-care claims costs ($49,341 vs $19,032, P < .001). To justify additional costs, ALBC would need to prevent infection in one of every 101 patients. ConclusionRoutine use of ALBC in primary TKA is not cost-effective, adding $299 to the cost of episode of care without a reduction in PJI rate. Further study is needed to determine whether select use of ALBC would be justified in high-risk patients.