Sensitive and accurate measures of osteolysis around TKR are needed to enhance clinical management and assist in planning revision surgery. Therefore, our aim was to examine, in a cadaver model of osteolysis around TKR, the sensitivity of detection and the accuracy of measuring osteolysis using Xray, CT and MRI. Fifty-four simulated osteolytic lesions were created around six cadaver knees implanted with either a cemented or cementless TKR. Twenty-four lesions were created in the femur and thirty in the tibia ranging in size from 0.7 cm3 to 14 cm3. Standard anteroposterior and lateral fluoroscopically guided radiographs, CT and MRI scans with metal reduction protocols were taken of the knees prior to the creation of lesions and at every stage as the lesion sizes were enlarged. The location, number and size of the lesions from images obtained by each method were recorded. The sensitivity of osteolytic lesion detection was 44% for plain radiographs, 92% for CT and 94% for MRI. On plain radiographs, 54% of lesions in the femur and 37% of lesions in the tibia were detected. None of the six posterior lesions created in the tibia were detected on the AP radiographs; however, three of these six lesions were detected on the lateral radiographs. CT was able to detect lesions of all sizes, except for four lesions in the posterior tibia (mean volume of 1.2 cm3, range 1.06–1.47 cm3). Likewise, MRI was very sensitive in detecting lesions of all sizes, with the exception of three lesions, two of which were in the femur and one was in the medial condyle of the tibia (mean volume of 1.9 cm3, range 1.09–3.14 cm3). Notably, all six posterior tibial lesions, which could not be detected using AP radiographs, were detected by MRI. This study demonstrates the high sensitivity of both CT and MRI (which uses no ionising radiation) to detect simulated knee osteolysis and can therefore be used to detect and monitor progression of osteolysis around TKR. The study also shows the limitations of plain radiographs to assess osteolysis.