The eastern margin of the Tibetan Plateau, a global biodiversity hotspot, is threatened by habitat degradation. Conservation actions are required in this region, but limited knowledge of large and medium-sized mammals is hampering conservation planning. Using 149 camera traps, we surveyed large and medium-sized mammals in Xionglongxi Provincial Nature Reserve and adjacent areas, on the eastern margin of the Tibetan Plateau, during September 2016–May 2017. We obtained 5,752 independent captures of 29 large and medium-sized mammal species, including 13 that are globally threatened and 22 that are nationally threatened in China. Carnivores were especially diverse, with 16 species recorded. Of particular significance was our detection of seven felid species, including the leopard Panthera pardus and the snow leopard Panthera uncia. Our record of the Chinese mountain cat Felis bieti extends the known range of this species. We documented new upper elevation limits for eight species. There was elevational overlap between the leopard and the snow leopard, suggesting potential competition between the two species. The grey wolf Canis lupus and the leopard were the dominant predators, and the woolly hare Lepus oiostolus and several species of ungulates were the most frequently photographed prey species. The study area maintains a significant community of large and medium-sized mammals, which is more diverse than in other areas on the eastern edge of the Tibetan Plateau. We recommend the establishment of a larger nature reserve of national protection status in the region of the Xionglongxi Provincial Nature Reserve, to protect the unique subalpine and alpine ecosystems in this area.