This study aims to present a series of cases reports of- knee arthritis occurring following COVID-19 RNA vaccination and to examine the potential role of these Spike protein-based RNA vaccines in the development of this arthritis. Although musculoskeletal disorders have been reported in connection with COVID-19 vaccines, post-vaccination arthritis is not yet listed. Given the different and specific mechanisms of Spike protein-based RNA vaccines and viral vector-based DNA vaccines, we report 7 cases that question the role of COVID-19 vaccines in the onset of early or late-onset knee arthritis observed following one or more injections. All patients (5 early onset and 2 late-onset cases) were examined in the same department and underwent a comprehensive assessment to investigate the usual causes of unilateral or bilateral oligoarthritis; none of them had a previous predisposition to rheumatic disease. No inflammatory rheumatic disease was detected, nor did any develop after a follow-up period of at least 24 months. A double-check of medical histories (both prior to and following diagnosis) was carried out by consulting the general medical database for all patients described. Post-vaccination serological monitoring of blood and synovial fluid to detect the presence of anti-spike antibodies has been requested for all patients and a synovial biopsy was performed in four of them. All patients showed improvement following low-dose prednisolone treatment within two months, but in some patients the symptoms persist. Anti-Spike antibody levels were found to be elevated in blood and synovial fluid samples from all patients. Synovial biopsies reveal chronic histiocytic (CD68+) and plasmocytic infiltration (CD3+) accompanied by neovascularisation. The similar timeline, progression and clinical manifestations of this knee arthritis might suggest a pathogenic role for the spike protein and/or an overproduction of anti-spike antibodies following mRNA vaccination.