The design of distillation systems has typically been carried out based on economic objectives, driven by operating costs and energy requirements. Other aspects, such as safety considerations, are carried out after the design has been developed. In this work, the application of risk measurements as part of the design of distillation systems is presented. Principles of quantitative risk analysis together with economic objectives are used for the design of two types of distillation arrangements, namely conventional distillation and multi-effect distillation. Two types of mixtures that address different safety implications are taken as case studies. Their operating costs and safety implications as part of their separation characteristics are quantified. It is shown how the application of the methodology here presented allows the detection of critical design variables not only from economic terms but also as far as their safety implications. The analysis provides the basis for the design of inherently safer distillation systems. (C) 2014 Elsevier Ltd. All rights reserved.