AbstractPurposeThe purpose of this study was to analyse the impact on peri‐prosthetic joint infection (PJI) rate and prosthetic survival using antibiotic‐loaded bone cement (ALBC) versus plain cement during total knee arthroplasty (TKA).MethodsA retrospective cohort study was conducted. The main data source was the Catalan Arthroplasty Register (RACat). TKAs with surgery date between 1 January 2011 and 31 December 2020 were analysed and followed up until 31 December 2023. The main variable of interest was the type of cement (ALBC vs. plain cement), and several endpoints (septic revision, aseptic revision, and all‐cause revision) were considered. The analysed outcomes were revision rates, survival rates and risk factors' hazard ratios (HR).ResultsA total of 22,781 TKAs were analysed, 13,125 (57.6%) of them with plain cement and 9656 (42.4%) with ALBC. The septic revision rate was lower in the ALBC group after 3 months of follow‐up (0.52% vs. 0.78%, p value = 0.04). Prosthetic survival with respect to the aseptic revision endpoint was also higher for the ALBC group during the whole follow‐up period (~158 months). Regarding risk factors for infection, ALBC showed a protective effect, HR: 0.53 (0.44, 0.63), while sex (being male) and the analysed comorbidities increased the risk.ConclusionsALBC is associated with a reduction in both the septic revision and the aseptic revision rate after TKA, and thus with higher prosthetic survival.Level of EvidenceLevel III, Therapeutic, retrospective.