A new design approach is introduced to prevent the propagation of collapse in buildings after major initial failures. The method, inspired by how lizards shed their tails to escape predators, ensures that specific structural elements fail before the most critical components, isolating the collapse and preventing it from spreading. This approach is validated through experimental tests on a full-scale precast concrete building. The study shows that conventional designs, which focus on connectivity to prevent collapse initiation, can lead to total collapse when large initial failures occur. The proposed hierarchy-based collapse isolation design ensures that connections fail before columns, limiting the collapse to affected areas. This design was tested on a 15m x 12m precast concrete building with two 2.6m-high floors. The results demonstrate that the design effectively isolates collapse after large initial failures while still preventing collapse initiation after smaller ones. The study highlights the importance of designing buildings to withstand extreme events and emphasizes the need for robust structures that can resist initial damage. The findings suggest that incorporating hierarchy-based collapse isolation can significantly enhance building resilience and reduce the risk of catastrophic collapse.A new design approach is introduced to prevent the propagation of collapse in buildings after major initial failures. The method, inspired by how lizards shed their tails to escape predators, ensures that specific structural elements fail before the most critical components, isolating the collapse and preventing it from spreading. This approach is validated through experimental tests on a full-scale precast concrete building. The study shows that conventional designs, which focus on connectivity to prevent collapse initiation, can lead to total collapse when large initial failures occur. The proposed hierarchy-based collapse isolation design ensures that connections fail before columns, limiting the collapse to affected areas. This design was tested on a 15m x 12m precast concrete building with two 2.6m-high floors. The results demonstrate that the design effectively isolates collapse after large initial failures while still preventing collapse initiation after smaller ones. The study highlights the importance of designing buildings to withstand extreme events and emphasizes the need for robust structures that can resist initial damage. The findings suggest that incorporating hierarchy-based collapse isolation can significantly enhance building resilience and reduce the risk of catastrophic collapse.