As a consequence of an ever-growing population land is getting scarcer, especially in urban areas. In the last decade, the space available above transport infrastructure - such as roads and railway tracks - and existing buildings is being exploited more and more frequently in city centres. The safety issue in such projects should be considered as the utmost important issue and should therefore not be underestimated. Usually, a large number of people and several multiple risk dimensions are involved. Due to the complexity and interrelationships, a small accident, like a fire in the building or the infrastructure, can easily lead to a major disaster. In The Netherlands, the safety issue is an extra difficulty, because of transport of hazardous materials. Several places are characterised by exceeding the acceptability and tolerability criterion of safety. Remarkably, these areas are exactly the areas for which the Fifth National Policy Document on Spatial Planning of the Netherlands desires intensification, combination and transformation. In this thesis, physical safety is assessed in these projects for the construction and the exploitation stage. This thesis provides a framework for the design of physical safety aspects in multiple use of space projects.