Our aim was to compare the assessment of periprosthetic osteolysis around total knee arthroplasties using digital images against film-screen images. Simulated osteolytic lesions were created around 3 cadaveric total knee arthroplasties images acquired using fluoroscopic-assisted radiography and Computed Tomography. Three surgeons reviewed the film-screen images (AP/Lateral, Oblique, and Computed Tomography (CAT)) and the same images digitally. Combinations of 2 or more images that included the AP/Lateral views had superior performance in both film-screen and digital imaging to AP/Lateral views alone, except for the digital AP/Lateral/OBL combination. Lesion detection and volume appreciation were superior for film versus digital assessment for most angles. The addition of obliques to assessment using digital imaging improved performance, but film-screen remained superior to digital imaging for assessment of periprosthetic osteolysis.