Catastrophic events generate cascading and synergistic infrastructure failures that will produce unanticipated response requirements. Infrastructure failures not only influence the demands for services and commodities but also the mobility and capability of response organisations. This project modelled a catastrophic earthquake (M7.7) in the New Madrid Seismic Zone (NMSZ). The US Geological Survey (USGS) has estimated the probability of a major NMSZ (M7.5 to M8.0) earthquake has a 7% to 10% probability of occurring in a 50-year period (US Geological Survey, 2006). The effects of such an event will cause tens of thousands of injuries and thousands of deaths. Over seven million people will experience disruptions in lifelines and two million will seek shelter. Direct impacts will be felt in the Central USA with ripple effects evident throughout the nation. Damage to critical infrastructure and lifelines will severely impair response and recovery efforts. The comprehensive modelling performed in this study provides not only direct damages to physical inventory, but also estimates the social impacts and response requirements. These inputs provide emergency managers the information required to plan and develop strategies to respond to such an event.