Craig Della Valle, MD, Javad Parvizi, MD, Thomas W. Bauer, MD, PhD, Paul E. DiCesare, MD, Richard Parker Evans, MD, John Segreti, MD, Mark Spangehl, MD, William C. Watters, III, MD, Michael Keith, MD, Charles M. Turkelson, PhD, Janet L. Wies, MPH, Patrick Sluka, MPH and Kristin Hitchcock, MIS J Am Acad Orthop Surg, Vol 18, No 12, December 2010 This clinical practice guideline was approved by the American Academy of Orthopaedic Surgeons on June 18, 2010. The complete guideline, which includes all tables, figures, and appendices, is available at http://www.aaos.org/research/guidelines/PJIguideline.asp. No preferred test for diagnosis of periprosthetic joint infection exists, and the algorithm for the workup of patients suspected of infection remains unclear. The work group evaluated the available literature to determine the role of each diagnostic modality and devise a practical algorithm that allows physicians to reach diagnosis of periprosthetic joint infection. Ten of the 15 recommendations have strong or moderate evidence in support. These include matters involving erythrocyte sedimentation rate and C-reactive protein level testing, knee and hip aspiration, and stopping the use of antibiotics prior to obtaining intra-articular cultures. The group recommends against the use of intraoperative Gram stain but does recommend the use of frozen sections of peri-implant tissues in reoperation patients in whom infection has not been established, as well as multiple cultures in reoperation patients being assessed for infection. The group recommends against initiating antibiotic treatment in patients with suspected infection until after joint cultures have been obtained, but recommends that prophylactic preoperative antibiotics not be withheld in patients at lower probability for infection.