Infection of total knee arthroplasty (TKA) is a challenge in orthopedic surgery. In literature TKA infection is classified according to the time after surgery: acute postoperative; late chronic; acute hematogenous; positive intraoperative microbiological growth. The purpose of this study is to present the results of the use of a preformed antibiotic-loaded spacer in TKA infections, treated by a two-stage revision procedure. A series of 19 consecutive patients (20 knees) with a diagnosis of infected TKA were treated from January 2003 to February 2012. Two-stage reimplantation protocols were completed only in 16 patients and these data were included in the study. We lost three patients at follow-up. An antibiotic-loaded preformed articulating polymethylmethacrylate spacer was applied. Patients were observed 1, 3, and 6 months postoperatively and then yearly for clinical and radiographic examination. The mean American Knee Society Score improved from 68.4 preoperatively (range, from 34 to 108) to 112.7 at final follow-up (range, from 49 to 180). The pain was evaluated as part of clinical score. It improved from an average of 19.3 preoperatively (range, from 10 to 30) to 34.3 at final follow-up (range, from 10 to 50). The average range of motion improved from 40.1 degrees (range, from 6 to 90 degrees) to 79.3 degrees (range, from 45 to 125 degrees). The use of the spacer allows obtaining a reduction of pain, an improvement of quality of life in the period of time between the two surgical stages and an easier reimplantation of TKA.