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Objectives: The Neanderthal patella differs from that of extant humans by being thicker anteroposteriorly and by having more symmetric medial and lateral articular facets. However, it is still unclear to what extent these differences affect knee kinesiology. We aim at assessing the endostructural conformation of Neanderthal patellae to reveal functionally related mechanical information comparatively to the extant human condition. In principle, we expect that the Neanderthal patella (i) shows a higher amount of cortical bone and (ii) a trabecular network organization distinct from the extant human condition., Materials and Methods: By using micro-focus X-ray tomography, we characterized the endostructure of six adult patellae from the OIS 5e Neanderthal site of Krapina, Croatia, the largest assemblage of human fossil patellae assessed so far, and compared their pattern to the configuration displayed by a sample of 22 recent humans., Results and Discussion: The first expectation is rejected, indicating that the patellar bone might have not followed the trend of generalized gracilization of the human postcranial skeleton occurred through the Upper Pleistocene. The second prediction is at least partially supported. In Krapina the trabecular network differs from the comparative sample by showing a higher medial density and by lacking a proximal reinforcement. Such conformation indicates similar load patterns exerted in Neanderthals and extant humans by the vastus lateralis, but not by the vastus medialis, with implications on the mediolateral stabilization of the knee joint. However, the patterns of structural variation of the patellar network remain to be assessed in other Neanderthal samples., (© 2023 The Authors. American Journal of Biological Anthropology published by Wiley Periodicals LLC.)