Background: High fever, knee swelling and pain after knee arthroplasty are often considered as symptoms of acute prosthetic joint infection. However, similar symptoms can also present as primary manifestations of adult-onset Still’s disease, which creates some interference in differential diagnosis. To our knowledge, this is the first published case of misdiagnosis of adult Still’s disease after total knee arthroplasty, who was initially misdiagnosed as an prosthetic joint infection due to the above-mentioned symptoms. The symptoms of the knee infection was not relieve after several revisions and continous antibiotic treatment. Finally, after several consultations and repeated evaluation it was diagnosed as adult-onset Still’s disease. Case presentation: A 77-year-old female who underwent bilateral total knee arthroplasty 6 years ago was admitted to our hospital with high fever, right knee effusion and painful knee. Based on the results of joint fluid aspiration and culture, we treated the right knee as acute hematogenous prosthetic joint infection. After three debridement and revision surgeries, the patient’s symptoms continued to persist. Subsequent manifestations of other symptoms such as typical rash and sore throat and laboratory examination suggested the possibility of adult-onset Still’s disease. So she underwent diagnostic steroid hormone therapy at the recommendation of a rheumatologist, and a final revision was performed after symptom was controlled. At the one-year follow-up, the patient’s symptoms completely resolved and the knee revision was functioning well. Conclusions: When joint swelling and pain occurs after knee arthroplasty, the possibility of joint infection should not only be considered, but rheumatic autoimmune diseases should also be differentiated. Because the manifestations of joint infection and rheumatic immune disease sometimes overlap highly, when reasonable treatment over a period of time fails to relieve symptoms and signs, we should notice subtle differences in symptoms and laborotary tests and look for other diagnostic possibilities in time. © 2020, The Author(s).