Persistence of populations may be uncertain for large carnivore species, especially for those established in human-dominated landscapes. Here, we studied the Eurasian lynx in Western Europe established in the Upper Rhine meta-population (i.e., Jura, Vosges-Palatinian and Black Forest populations) and the Alpine population. These populations are currently considered endangered or critically endangered due to high anthropogenic mortality, small population size and low genetic diversity, and isolation. We assessed lynx persistence over a 50-year time horizon by implementing a spatially-explicit individual-based model, while accounting for road mortality and habitat selection. Forecasts showed a steady growth rapidly reaching a more stable phase for the Alpine and Jura populations, and a more heterogeneous positive growth with less precision for the Vosges-Palatinian and Black Forest populations. Exchanges of individuals between populations were limited, the Jura population playing the role of a crossroad. Finally, the persistence of lynx in Western Europe seems likely on a large scale over the next 50 years. Indeed, simulations showed high female occupancy as well as average lynx density over the core areas of the four studied populations. Nevertheless, these results should be interpreted with the model limitations in mind, concerning the absence of movement barriers and inbreeding depression.