Periprosthetic gout flare is a rare arthritic condition after total knee arthroplasty, but the symptoms of gout may have often been mistaken as acute periprosthetic infection given their similarity. Misdiagnosis as periprosthetic infection can lead to unnecessary surgery, long-term dependence on anti-biotics, and even malfunction of the involved knee joint. Here, we report a case study of a patient with immunodeficiency condition of long-term oral glucocorticoid and diabetes mellitus, who had undergone a knee replacement 8 weeks before. The initial symptoms of fever and joint pain together with the dysfunction of her right knee with elevated inflammatory markers, such as increased serum leukocytes, erythrocyte sedimentation rate, C-reactive protein, and synovial cell counts led to a diagnosis of acute periprosthetic infection. Arthrocentesis and bacterial culture were performed preoperatively. According to the current Musculoskeletal Infection Society (MSIS) criteria for diagnosis of periprosthetic infection, the case was classified as periprosthetic infection and a prosthesis retained debridement surgery was performed. However we got negative culture results in all the pre-operative and intro-operative samples. The symptoms as well as the laboratory inflammatory markers improved shortly after the debridement surgery until the 11th day when all the similar systemic and local symptoms recurred. With a remedial crystal analysis of synovial fluid from the patient, gouty flare was found to be the cause of acute arthritis finally. Accor-dingly, after anti-gout medications were administrated, the symptoms associated with acute arthritis gra- dually subsided, and there was no recurrence during a 24-month follow-up. This article described the cli-nical manifestation, diagnosis and differential diagnosis, treatment of a case of periprosthetic gout. Although relatively rare, gout should be considered as a differential diagnosis in suspected periprosthetic infection. Current criteria for periprosthetic infection can not exclude the diagnosis of periprosthetic gout flare, it is therefore imperative that the analysis of joint aspirate for crystals be conducted to determine the correct course of treatment, or unnecessary surgical procedure may be performed in periprosthetic gout case.