This study determined the accuracy of plain radiography in detecting osteolytic lesions around total knee prostheses compared to multi-detector computed tomography (CT). Thirty-one patients diagnosed with periprosthetic osteolysis by multi-detector CT after total knee arthroplasty (TKA) were studied. Computed tomography for each patient was retrospectively reviewed in a blinded fashion. The plain radiographs for each patient that had been obtained prior to CT were reviewed in the same manner. The results of the CT were compared with the results of the radiographs. The number, size, and location of the lesions were compared. The multi-detector CT detected 48 lesions in 31 knees: 40 tibial lesions, 4 femoral lesions, and 4 patellar lesions. Radiographic diagnosis was made in 6 of the 40 tibial lesions, 2 of the 4 femoral lesions, and 0 of the 4 patellar lesions. Plain radiographs are inadequate for evaluating periprosthetic osteolysis in TKA with only 8 (17%) of 48 lesions detected by multi-detector CT visible on the standard radiographs. Multi-detector CT provides the surgeon with a diagnostic and preoperative planning tool when osteolysis is suspected.