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Prosthetic joint infection (PJI) remains a challenge to treat. We utilized intra-articular administration of antibiotics for the treatment of two infected total knee arthroplasties. The first patient developed an early post-operative infection with persistent wound drainage within a week after primary total knee arthroplasty (TKA). The second patient had an acute hematogenous infection, presenting with knee pain with a preceding history of leg cellulitis, one year after a primary TKA. Both patients were treated with surgical debridement, exchange of tibial insert with implant retention, and intra-articular administration of vancomycin for six weeks. Treatment was successful for both patients, with preservation of knee function and no recurrence of infection after one year. We reported two cases of PJI treated with direct intra-articular antibiotic administration following surgical debridement and implant retention.