Restoring populations of large mammals in human-dominated landscapes requires careful planning of conservation strategies. To support such planning for the European bison (Bison bonasus), Europe’s largest land mammal currently constrained to small and isolated populations, we parameterized an individual-based, spatially-explicit metapopulation model. We then systematically assessed the impacts of three conservation interventions: 1) connectivity restoration with wildlife overpasses, 2) additional reintroductions, and 3) reduced supplementary feeding to encourage dispersal. Our baseline model projected a doubling of bison abundance in Central Europe within 30 years to >2250 females (in 20 occupied habitat patches), reaching >4300 females (38 patches) within 100 years. Yet subpopulations often remained isolated, highlighting the need for interventions to increase connectivity to prevent a further erosion of already low genetic diversity. Of the interventions we tested, reintroductions were most effective (5% abundance increase, 10% patch occupancy increase, on average, after 50 years) and helped establish larger metapopulations that are important for maintaining genetic diversity. Individual wildlife overpasses had a small effect (1% range increase). Reducing supplementary feeding did not promote range expansion and slightly slowed population growth. We found that the five extant subpopulations in north-eastern Poland could form a viable metapopulation and identified two additional promising regions for such metapopulations: (1) Western Poland/Eastern Germany, and (2) the Eastern Carpathians in Poland/Slovakia. Overall, our findings underscore the potential for European megafauna recovery, highlight the key role of reintroductions to help megafauna reclaim their historical ranges, and can guide more fine-scale assessments of the social-ecological feasibility of such recoveries.