Diffraction-enhanced imaging (DEI) is a radiographic technology that harnesses the X-ray refraction and scatter rejection properties that are not available with conventional radiography. Here, we test the efficacy of planar DEI to render images from which cartilage degeneration, characteristic of osteoarthritis, can be detected. DEI was carried out on human cadaveric intact knee joints at the X-15 beamline at the National Synchrotron Light Source. The gross specimens and the DEI images were graded separately for levels of cartilage degeneration on six individual surfaces: anterior and posterior femoral and tibial on both medial and lateral sides. There was a significant correlation between the actual levels of cartilage degeneration and what was observed in their respective DEI images (P < 0.05) for all six articular surfaces. Some articular surfaces (patellar surfaces, in particular) could not be visualized because of overlap with superimposed bone. Sensitivity for the graded articular surfaces was 0.73 and specificity was 0.92 (Grade 0 being no lesion and Grades 1–6 being increasing gradations of lesions). Chondrocalcinosis was also observed in DEI images to a far greater extent compared with the conventional radiographs. DEI renders images that are significantly correlated with their actual gross morphology. Detection of lesions was better for more severe grades of degeneration than for partial focal lesions. Although some articular surfaces could not be visualized because of superimposed bone, we feel that DEI has potential for the diagnosis of cartilage lesions and chondrocalcinosis. Clin. Anat. 26:621–629, 2013. © 2012 Wiley Periodicals, Inc.