A proportion of patients with hip and knee prosthetic joint infection (PJI) undergo multiple revisions with the aim of eradicating infection and improving quality of life. The aim of this study was to describe the microbiology cultured from multiply revised hip and knee replacement procedures to guide antimicrobial therapy at the time of surgery. Patients and methods: Consecutive patients were retrospectively identified from databases at two specialist orthopaedic centres in the United Kingdom between 2011 and 2019. Patient were included who had undergone repeat-revision total knee replacement (TKR) or total hip replacement (THR) for infection, following an initial failed revision for infection. Results: A total of 106 patients were identified. Of these patients, 74 underwent revision TKR and 32 underwent revision THR. The mean age at first revision was 67years (SD 10). The Charlson comorbidity index was 2 for 31 patients, 3-4 for 57 patients, and 5 for 18 patients. All patients underwent at least two revisions, 73 patients received three, 47 patients received four, 31 patients received five, and 21 patients received at least six. After six revisions, 90 % of patients had different organisms cultured compared with the initial revision, and 53 % of organisms were multidrug resistant. The most frequent organisms at each revision were coagulase-negative Staphylococcus (36 %) and Staphylococcus aureus (19 %). Fungus was cultured from 3 % of revisions, and 21 % of infections were polymicrobial. Conclusion: Patients undergoing multiple revisions for PJI are highly likely to experience a change in organism, with 90 % of patients having a different organism cultured by their sixth revision. It is therefore important to administer empirical antibiotics at each subsequent revision, taking into account known drug resistance from previous cultures. Our results do not support the routine use of empirical antifungals.