Abstract:[Objective] Periprosthetic joint infection (PJI) is a terrible complication after total hip arthroplasty (THA). Managing culture-negative patients with a PJI poses a greater challenge to surgeons. The objective of this study is to explore clinical characters and possible risk factors of culture negative periprosthetic joint infection patients. Long-term clinical results and treatment outcome were compared in two patient groups undergoing two-stage revision arthroplasty. [Methods] We retrospectively reviewed Consecutive patients who underwent a two-stage revision THA for chronic infection between 2012 and 2018 from the database. According to the diagnostic criteria of PJI, Two groups including CN-PJI group and CP-PJI group were identified for this study. Information such as the demographics, laboratory findings, clinical outcomes and recurrence of infection were analyzed. All patients were followed at 1 year after revision surgery. [Results] 33 patients were divided into CP-PJI group and 16 patients were divided into CN-PJI group. CN-PJIs were associated with older age, diabetes and pre-operative antibiotic treatment, and pre-operative antibiotics are the most significant risk factors. The CN-PJI group showed a significantly higher incidence of prior antibiotic use (p=0.0067) and lower serum C-reactive protein (CRP) and ESR level (p<0.05) than the CP-PJI group. In CN-PJI group the prosthetic median survival time 43 months (2-108 months), which has a significant longer survival span than CP group (prosthetic median survival time 12 months, 15d-48 months). The most common pathogens of PJI are Staphylococcus aureus and coagulase-negative staphylococci (60.6%). There was no case of treatment failure or major complication in CN-PJI group. The rate of re-infection in the CN-PJI group was lower. [Conclusion] Two-stage revision had a high success rate for eradication of periprosthetic hip joint infection. Furthermore, the culture negativity may not necessarily be a negative prognostic factor for periprosthetic joint infection.