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Introduction Diagnostic and therapeutic management of patients with periprosthetic joint infections (PJIs) remains challenging. This national cohort aims to describe the epidemiology, clinical phenotypes, management strategies and outcomes of patients with PJI.Methods and analysis This is a national, multicentre, prospective, longitudinal, observational cohort study of patients who underwent revision for PJI of the hip, knee, shoulder, elbow or ankle. Participating centres are university or non-university tertiary healthcare facilities located in Switzerland. Episodes include likely and confirmed PJI, as defined by the European Bone and Joint Infection Society criteria. During routine clinical visits around revision surgery, data are collected and patients are followed-up thereafter for a minimum of 2 years. The primary objective is infection outcome and secondary objectives include functional outcome and patient satisfaction and evaluation of host, infection, microbiological and treatment factors associated with treatment failure and poor functional outcomes, both in the overall population and across subgroups. A minimum of 329 patients would be needed to have sufficient statistical power to carry out these analyses.Ethics and dissemination Ethical approval has been granted by the Research Ethics Committee under protocol number 2021-01791. All patients provide written informed consent for inclusion in the study. Study findings will be disseminated through publications in peer-reviewed journals and presented at national and international conferences in the fields of orthopaedics, infectious diseases and microbiology. We plan to leverage the platform within the cohort to conduct future studies and interventional trials.Trial registration number NCT07473089.