The impact of the 2004 Indian Ocean Tsunami on multiple tourism destinations was a striking reminder of the vulnerability of tourism-dependent destination communities to shocks and stressors. However, the causal drivers of destination vulnerability remain under-researched. Furthermore, there are few studies that systematically apply and test the usefulness of new theoretical frameworks in assessing real-world problems like vulnerability to natural hazards. This crucial step in social theory development is often overlooked. In this paper we redress these fundamental gaps by “operationalising” the new Destination Sustainability Framework (DSF). The DSF is used to guide a case study-based comparative destination vulnerability assessment (DVA) of the tsunami-affected destinations of Khao Lak, Patong and Phi Phi Don in Thailand to better understand destination vulnerability and its evolution in different places and developmental contexts. The findings indicate that destination vulnerability is created and perpetuated by a combination of multiple, dynamic and interacting factors, including geographical exposure, destination-specific development characteristics, social structures and governance processes. Underlying these factors and processes are competing stakeholder agendas and actions, historically-embedded cultural norms, institutional preferences and power structures that entrench and perpetuate unequal access to resources, all of which play out at multiple scales of social organisation over time.