The tragic accidents at Flixborough and Bhopal have led to the development of new legislation concerning the design and operation of chemical plants. In addition, the growing concern with safety and environmental issues places many new demands upon the designer. Process plant layout, as an important step in the design of chemical plants, is effected by these demands. This paper presents a new approach to process plant layout that integrates safety and economics. In this approach, the cost of a layout is a function of piping cost, land cost, financial risk, and protection devices cost. The financial risk term captures the risk of unsafe plants and can be expressed as the expected losses if major accidents happen (i.e., fires or explosions). The proposed approach is a mixed-integer nonlinear optimization problem (MINLP) that identifies attractive layouts by minimizing overall costs. This approach gives the coordinates of each unit, an estimate for the total piping length, the amount of land occupied, and the safety devices that have to be installed at each unit.