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Background Although periprosthetic joint infection (PJI) can affect multiple joints concurrently, the majority of patients with multiple prosthetic joints present with PJI of a single joint. Data regarding the optimal management of these patients are limited. We aimed to identify the prevalence, risk factors for a subsequent PJI, and clinical circumstances of PJI in patients with multiple prosthetic joints. Methods We retrospectively reviewed the clinical records of 197 patients with ≥2 total joint prostheses in place who presented with