urpose: periprosthetic joint infection (PJI) accounts for 25% of failed total knee arthroplasties (TKAs) and 15% of failed total hip arthroplasties (THAs). The purpose of the present study was to design a multidi- sciplinary diagnostic algorithm to detect a PJI as cause of a painful TKA or THA. Methods: from April 2010 to October 2012, 111 patients with suspected PJI were evaluated. The study group comprised 75 females and 36 males with an ave- rage age of 71 years (range, 48 to 94 years). Eighty- four patients had a painful THA, while 27 reported a painful TKA. The stepwise diagnostic algorithm, applied in all the patients, included: measurement of serum C-reactive protein (CRP) and erythrocyte sedi- mentation rate (ESR) levels; imaging studies, inclu- ding standard radiological examination, standard tech- netium-99m-methylene diphosphonate (MDP) bone scan (if positive, confirmation by LeukoScan was obtained); and joint aspiration with analysis of syno- vial fluid