Background and purpose Optical coherence tomography (OCT) is a light-based imaging technique suitable for depiction of thin tissue layers such as articular cartilage. Quantification of results and direct comparison with a reference standard is needed to confirm the role of OCT in cartilage evaluation.Materials and methods Goat talus articular cartilage repair was assessed quantitatively with OCT and compared with histopathology using semi-automated analysis software. Osteochondral defects were created centrally in goat tali with subsequent healing over 24 weeks. After sacrifice, the tali were analyzed using OCT and processed into histopathology slides. Cartilage thickness, repair tissue area, and surface roughness were measured. Also, light attenuation coefficient measurements were performed to assess differences in the properties of healthy tissue and repair tissue.Results Intra-class correlation coefficients for resemblance between the 2 techniques were 0.95 (p < 0.001) for thickness, 0.73 (p = 0.002) for repair tissue area, and 0.63 (p = 0.015) for surface roughness. Light attenuation differed significantly between healthy cartilage (8.2 (SD 3.9) mm-1) and repair tissue (2.8 (SD 1.5) mm-1) (p < 0.001).Interpretation Compared to histopathology as the standard reference method, OCT is a reproducible technique in quantitative analysis of goat talus articular cartilage, especially when assessing cartilage thickness and to a lesser extent when measuring repair tissue area and surface roughness. Moreover, differences in local light attenuation suggest measurable variation in tissue structure, enhancing the clinical applicability of quantitative measurements from cartilage OCT images.