Mass casualty incidents are a concern in many urban areas. A community’s ability to cope with such events depends on the capacities and capabilities of its hospitals for handling a sudden surge in demand of patients with resource-intensive and specialized medical needs. This paper uses a whole-hospital simulation model to replicate medical staff, resources, and space for the purpose of investigating hospital responsiveness to mass casualty incidents. It provides details of probable demand patterns of different mass casualty incident types in terms of patient categories and arrival patterns, and accounts for related transient system behavior over the response period. Using the layout of a typical urban hospital, it investigates a hospital’s capacity and capability to handle mass casualty incidents of various sizes with various characteristics, and assesses the effectiveness of designed demand management and capacity-expansion strategies. Average performance improvements gained through capacity-expansion strategies are quantified and best response actions are identified. Capacity-expansion strategies were found to have superadditive benefits when combined. In fact, an acceptable service level could be achieved by implementing only 2 to 3 of the 9 studied enhancement strategies. (Disaster Med Public Health Preparedness. 2018;12:778-790)